Publications by authors named "Chiara Sarlo"

25 Publications

  • Page 1 of 1

The IPSS-R more accurately captures fatigue severity of newly diagnosed patients with myelodysplastic syndromes compared with the IPSS index.

Leukemia 2020 09 21;34(9):2451-2459. Epub 2020 Feb 21.

Data Center and Health Outcomes Research Unit, Italian Group for Adult Haematologic Diseases (GIMEMA), Rome, Italy.

We aimed to compare fatigue of newly diagnosed patients with myelodysplastic syndromes (MDS) with that of the general population (GP). We also investigated the ability of the IPSS and IPSS-R to capture severity of patient-reported fatigue at diagnostic workup. A sample of 927 newly diagnosed patients with MDS was consecutively enrolled in a large international observational study and all patients completed the FACIT-Fatigue questionnaire at baseline. Fatigue was compared with that of the GP (N = 1075) and a 3-point difference in mean scores was considered as clinically meaningful. Fatigue of MDS patients was on average 4.6 points below the mean of the GP (95% CI, -5.9 to -3.2, p < 0.001), reflecting clinically meaningful worse fatigue. Unlike the IPSS, the IPSS-R identified clearly distinct subgroups with regard to burden of fatigue. Mean scores differences compared with GP ranged from nonclinically relevant for very low risk (Δ = -1.8, 95% CI, -4.0 to 0.5, p = 0.119) to large clinically meaningful differences for very high-risk IPSS-R patients (Δ = -8.2, 95% CI, -10.3 to -6.2, p < 0.001). At diagnostic workup, fatigue of MDS is clinically meaningful worse than that reported by the GP. Compared with the IPSS classification, the IPSS-R provides a better stratification of patients with regard to fatigue severity.
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http://dx.doi.org/10.1038/s41375-020-0746-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509847PMC
September 2020

Pulmonary infections in patients with myelodysplastic syndromes receiving frontline azacytidine treatment.

Hematol Oncol 2020 Apr 23;38(2):189-196. Epub 2020 Jan 23.

Hematology, Dipartimento Medicina Traslazionale e di Precisione, AOU Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

Pulmonary infections (PIs) are a major complication of patients with myelodysplastic syndromes (MDS). We retrospectively evaluated 234 MDS patients treated with azacytidine (AZA). The total number of AZA cycles was 2886 (median 8 cycles per patient). There were 111 episodes of PI (3.8% of AZA cycles) in 81 patients (34.6%). PIs were considered of fungal origin in 27 cases (24.3%), associated to bacteremia in 11 cases (9.9%), to influenza infection in two cases (1.8%) and of unknown origin in the remaining 71 cases (64.0%). Forty-five PI episodes were documented in cycles 1 to 4 of AZA (5.1% of 875 cycles) and the remaining 66 episodes beyond the fourth cycle (3.2% of 2011 cycles) (P = .017). Overall, a fungal PI was documented in 13/875 (1.5%) cycles 1 to 4 and in 13/2011 (0.6%) cycles beyond the fourth cycle (P = .001). A baseline chronic pulmonary disease was significantly associated to a higher risk of severe PIs. In the survival analysis, cases of PI in patients who progressed to acute leukemia (PAL) were excluded, in view of the predominant influence of PAL on the outcome of the patients. A PI unrelated to PAL documented during the first 4 AZA cycles was an independent factor predicting lower survival (OR, 2.13; 95% CI, 1.37-3.33; P = .001). In conclusion, PIs are common in MDS patients receiving AZA, in particular during the first cycles of treatment and are associated with an unfavorable outcome. The results of our study raise the issue of the need of a tailored infection prevention strategy.
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http://dx.doi.org/10.1002/hon.2710DOI Listing
April 2020

Clinical significance of occult central nervous system disease in adult acute lymphoblastic leukemia. A multicenter report from the Campus ALL Network.

Haematologica 2021 01 1;106(1):39-45. Epub 2021 Jan 1.

Dipartimento di Medicina Molecolare, Universita' Sapienza, Roma.

In acute lymphoblastic leukemia, flow cytometry detects more accurately leukemic cells in patients' cerebrospinal fluid compared to conventional cytology. However, the clinical significance of flow cytometry positivity with a negative cytology - occult central nervous system disease - is not clear. In the framework of the national Campus ALL program, we retrospectively evaluated the incidence of occult central nervous system disease and its impact on outcome in 240 adult patients with newly diagnosed acute lymphoblastic leukemia. All cerebrospinal fluid samples were investigated by conventional cytology and flow cytometry. The presence of ≥10 phenotypically abnormal events, forming a cluster, was considered as flow cytometry positivity. No central nervous system involvement was documented in 179 patients, while 18 were positive by conventional morphology and 43 were occult central nervous system disease positive. The relapse rate was significantly lower in central nervous system disease negative patients and the disease-free and overall survival were significantly longer in central nervous system disease negative patients than in those with manifest or occult central nervous system disease positive. In multivariate analysis, the status of manifest and occult central nervous system disease positivity was independently associated with a worse overall survival. In conclusion, we demonstrate that in adult acute lymphoblastic leukemia patients at diagnosis flow cytometry can detect occult central nervous system disease at high sensitivity and that the status of occult central nervous system disease positivity is associated with an adverse outcome. (Clinicaltrials.gov NCT03803670).
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http://dx.doi.org/10.3324/haematol.2019.231704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776237PMC
January 2021

Gonadal Function Recovery and Fertility in Women Treated with Chemo- and/or Radiotherapy for Hodgkin's and Non-Hodgkin Lymphoma.

Chemotherapy 2019 22;64(1):36-41. Epub 2019 May 22.

Unit of Hematology, AUO Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.

Background: Fertility and gonadal function represent one of the most important aspects for long-term lymphoma survivors.

Aims: The aim of our study was to determine possible risk factors, such as age at treatment, chemotherapeutic regimen, protection with oral contraceptives (OCs), and gonadotropin-releasing hormone (GnRH) analogues in female patients treated for Hodgkin's lymphoma (HL) or non-Hodgkin lymphoma (NHL) at a reproductive age.

Methods: Patients between the age of 16 and 50 years at the time of HL or NHL diagnosis were selected. Eligible patients were requested to respond to a questionnaire by phone interview about fertility, menstrual status, sexual aspects, and treatment with OCs or GnRH analogues during chemotherapy.

Results: The resumption of menstrual activity was associated with the use of the OCs and GnRH analogues during chemotherapy (p = 0.008 and 0.034, respectively). At univariate analysis, the use of OCs during chemotherapy was associated with a lower risk of amenorrhea (prevalence ratio [PR] = 0.37; 95% CI 0.17-0.82). A higher age at the time of treatment correlated positively with therapy-induced amenorrhea, with a difference of 12.8 years between the mean age at diagnosis of the women with therapy-induced amenorrhea and those who resumed their menses. Amenorrhea was significantly higher in women receiving R-CHOP than in women treated with ABVD (PR = 6.00; 95% CI 2.32-15.54). Moreover, NHL had an infertility PR of 1.51 (95% CI 0.86-2.45) at multivariate analysis compared to HL.

Conclusions: This study suggests a possible role of pharmacological prophylaxis with OCs and GnRH analogues.
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http://dx.doi.org/10.1159/000499535DOI Listing
July 2019

Involvement of central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome.

Semin Hematol 2018 10 21;55(4):209-214. Epub 2018 Feb 21.

Hematology, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.

Incidence and effect on outcome of central nervous system (CNS) involvement in adult patients with acute myeloid leukemia (AML) is not clearly defined. To address this issue, 103 consecutive adult patients with newly diagnosed AML, regardless of neurologic symptoms, were submitted to a routine explorative lumbar puncture. Cerebrospinal fluid (CSF) samples were collected from 65 males and 38 females. All 103 CSF samples were examined by conventional cytology (CC) whereas 95 (92%) also by flow cytometry (FCM). At diagnosis, 70 patients (68%) were CNS negative (CNS-), whereas 33 (32%) were CNS positive (CNS+). In 11 of 33 (33%), CNS infiltration was documented either by CC or FCM , in 21 (67%) only by FCM. CNS positivity was significantly associated with a M4-M5 phenotype of the underlying AML (P = .0003) and with high levels of lactate dehydrogenase (P = .006). Overall, 80 of 103 (78%) achieved complete remission with no significant differences between CNS+ and CNS- patients. Five-year disease-free survival and overall survival were found to be shorter in CNS+ patients than in those CNS- (18% vs 50%, P = .006 and 19% vs 46%, P = .02, respectively). In multivariate analysis, CNS status and age were found to affect independently overall survival. In conclusion, the incidence of CNS involvement in adult patients with newly diagnosed AML is higher than expected. Regardless of neurologic symptoms, it should always be searched at diagnosis; CSF samples should routinely be investigated by FCM since a certain proportion of CNS involvements might remain undetected if examination is exclusively CC based.
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http://dx.doi.org/10.1053/j.seminhematol.2018.02.006DOI Listing
October 2018

Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients.

PLoS One 2018 23;13(7):e0200221. Epub 2018 Jul 23.

Laboratory of Virology, Campus Bio-Medico University, Rome, Italy.

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200221PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056038PMC
January 2019

Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications.

Mediterr J Hematol Infect Dis 2016 20;8(1):e2016052. Epub 2016 Oct 20.

Ematologia, Dipartimento di Biomedicina e Prevenzione, Università degli studi di Roma "Tor Vergata", Roma, Italia.

Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients' risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help to identify patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry(MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management.
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http://dx.doi.org/10.4084/MJHID.2016.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111512PMC
October 2016

'Real Life' experience in a 'difficult to treat' patient population of non-Hodgkin lymphomas using the R-COMP regimen.

Leuk Lymphoma 2016 12 11;57(12):2919-2922. Epub 2016 Apr 11.

a Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy Unit , University "Campus Bio-Medico" , Rome , Italy.

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http://dx.doi.org/10.3109/10428194.2016.1169410DOI Listing
December 2016

Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa.

Biomed Res Int 2015 6;2015:895105. Epub 2015 Sep 6.

Department of Haematology, University Campus Bio-Medico, Via A. del Portillo 200, 00128 Rome, Italy.

Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8-34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the "quality of life" matter is of primary importance.
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http://dx.doi.org/10.1155/2015/895105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575717PMC
July 2016

Minimal residual disease as biomarker for optimal biologic dosing of ARA-C in patients with acute myeloid leukemia.

Am J Hematol 2015 Feb 24;90(2):125-31. Epub 2014 Nov 24.

Ematologia, Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Roma, Italia.

We assessed by flow cytometry minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) given standard-dose (SDAC) and high-dose ARA-C (HDAC) regimens. Of 163 patients enrolled, 130 (median age, 45 years; range, 18-59 years) qualified for analysis, all achieving complete remission after treatment with SDAC (n = 78) or HDAC (n = 52) plus etoposide and daunorubicin. Consolidation consisted of intermediate-dose ARA-C and daunorubicin. MRD negativity was significantly more frequent in the SDAC vs. HDAC arm after both induction (37% vs. 15%, P = 0.007) and consolidation (44% vs. 18%, P = 0.002). Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5 × 10(-3) and 4 × 10(-3) (P = 0.033) after induction and 5.7 × 10(-4) and 2.9 × 10(-3) (P = 0.008) after consolidation. Based on ARA-C schedule and post-consolidation MRD status, the four patient groups (SDAC-MRD(-) , HDAC-MRD(-) , SDAC-MRD(+) , and HDAC-MRD(+) ) displayed 5-year overall survival rates of 60%, 33%, 24%, and 42% (P = 0.007), respectively, with 24%, 35%, 74%, and 48% (P < 0.0001) respective cumulative incidence of relapse estimates. MRD may serve as a biomarker for optimal biologic dosing of ARA-C, and SDAC regimen appears to yield more frequent MRD negativity.
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http://dx.doi.org/10.1002/ajh.23893DOI Listing
February 2015

High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

Ann Hematol 2014 Sep 22;93(9):1509-13. Epub 2014 Apr 22.

Cattedra di Ematologia, Dipartimento di Biopatologia e Prevenzione, Università Tor Vergata, Roma, Italia,

Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.
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http://dx.doi.org/10.1007/s00277-014-2080-6DOI Listing
September 2014

Infections increase the risk of central venous catheter-related thrombosis in adult acute myeloid leukemia.

Thromb Res 2013 Nov 16;132(5):511-4. Epub 2013 Aug 16.

Cattedra di Ematologia, Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Roma, Italia. Electronic address:

Introduction: Central venous catheters (CVC) related thrombosis (CRT) represents a well known complication in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy but the efficacy of antithrombotic prophylaxis still remains controversial.

Patients And Methods: We analyzed 71 consecutive AML patients whose CVC was inserted before each chemotherapy cycle for an overall number of 106 CVC placements. In 47/106 insertions, a prophylaxis with 100 IU/kg/day low molecular weight heparin (LMWH) was administered for 7 days after CVC insertion and additional 7 after CVC removal. This unconventional dose of LMWH, although higher than usual, appeared adequate for a short-course approach. LMWH was delivered regardless of the platelet (PLT) count once provided that it should have been maintained above 20 x 10(9)/L by transfusions.

Results: Of 106 insertions, we observed 19 (18%) episodes of CRT, 58 (54%) of sepsis and 50 (47%) infections of CVC-exit site with no difference between LMWH and no-LMWH group. Occurrence of CRT was significantly associated with CVC-exit site infections (14/19, p=0.01) and sepsis (16/19, p=0.005) with no difference between LMWH and no-LMWH group. In multivariate analysis, both CVC-exit site infections and sepsis were confirmed to be independent risk factors for CRT development.

Conclusion: Our retrospective study, although based on a small sample size, suggests that the occurrence of CVC-exit site infections and neutropenic sepsis following chemotherapy significantly increases the risk of CRT in AML, independently from the use of LMWH prophylaxis.
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http://dx.doi.org/10.1016/j.thromres.2013.08.007DOI Listing
November 2013

Treatment of acute myeloid leukemia with 20-30% bone marrow blasts.

Mediterr J Hematol Infect Dis 2013 3;5(1):e2013032. Epub 2013 Jun 3.

Cattedra di Ematologia, Università "Tor Vergata", Roma, Italia.

The transition of patients with ≥20% <30% bone marrow (BM) blast from the FAB category of myelodysplasia to the family of acute myeloid leukemia (AML) according to the recent WHO classification has not resolved the argument as to whether the natural history and responsiveness to therapy of these diseases is comparable to that of AML with > 30% BM blast. These controversies are even more manifest when it comes to elderly patients in whom concern for intensive chemotherapy (IC) related toxicity is the critical determinant for the therapeutic choice. In fact, due to concerns of treatment-related morbidity and mortality associated with delivery of IC, approximately only 30% of all patients ≥65 years are considered eligible for this approach. Therefore, a great deal of attention has been dedicated to alternative agents such as hypomethylators (azacitidine and decitabine). Actually, these agents have shown efficacy with reduced toxicity when administered to elderly patients with 20-30% BM blasts and not eligible for IC. In the present review, we will discuss the clinical results achieved in the treatment of elderly patients with 20%-30% BM blasts AML using intensive chemotherapy (IC) or hypomethylating agents. Overall, our survey of the literature suggests that only controlled, randomized, clinical trials will answer the question as to whether hypomethylating agents has the potential to substitute for IC even in elderly patients with an optimal functional status.
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http://dx.doi.org/10.4084/MJHID.2013.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684350PMC
June 2013

Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy.

Leuk Res Treatment 2013 28;2013:705714. Epub 2013 Apr 28.

Department of Hematology, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.

We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML), unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m(2) administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60-81) and the median number of cycles delivered was 2 (range 1-4). Of 13 evaluable patients, in 8 (61%), the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction. In 4 (50%) of these 8, a decrease by 37% of transfusion requirement was also observed (P = 0.009). Overall median survival was 4 months (range 0.25-10). Neurotoxicity was the most frequent adverse event with 7 of 13 (54%) patients experiencing grades 3-4 peripheral neuropathy. Neurotoxicity led to treatment discontinuation in 4 (57%) of 7. In conclusion, the observed anti-leukemic activity of bortezomib indicates that there is room for designing additional studies in which combination with other chemotherapeutic agents should be considered. Clinical registration no.: EUDRACT 2006-006923-38.
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http://dx.doi.org/10.1155/2013/705714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655652PMC
June 2013

Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia.

Blood 2010 Sep 14;116(13):2295-303. Epub 2010 Jun 14.

Hematology, Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, Italy.

A total of 143 adult acute myeloid leukemia (AML) patients with available karyotype (K) and FLT3 gene mutational status were assessed for minimal residual disease (MRD) by flow cytometry. Twenty-two (16%) patients had favorable, 115 (80%) intermediate, and 6 (4%) poor risk K; 19 of 129 (15%) carried FLT3-ITD mutation. Considering postconsolidation MRD status, patients with good/intermediate-risk K who were MRD(-) had 4-year relapse-free survival (RFS) of 70% and 63%, and overall survival (OS) of 84% and 67%, respectively. Patients with good- and intermediate-risk K who were MRD(+) had 4-year RFS of 15% and 17%, and OS of 38% and 23%, respectively (P < .001 for all comparisons). FLT3 wild-type patients achieving an MRD(-) status, had a better outcome than those who remained MRD(+) (4-year RFS, 54% vs 17% P < .001; OS, 60% vs 23%, P = .002). Such an approach redefined cytogenetic/genetic categories in 2 groups: (1) low-risk, including good/intermediate K-MRD(-) with 4-year RFS and OS of 58% and 73%, respectively; and (2) high risk, including poor-risk K, FLT3-ITD mutated cases, good/intermediate K-MRD(+) categories, with RFS and OS of 22% and 17%, respectively (P < .001 for all comparisons). In AML, the integrated evaluation of baseline prognosticators and MRD improves risk-assessment and optimizes postremission therapy.
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http://dx.doi.org/10.1182/blood-2009-12-258178DOI Listing
September 2010

Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia.

J Clin Oncol 2008 Oct 7;26(30):4944-51. Epub 2008 Jul 7.

Hematology, Policlinico Tor Vergata and Ospedale S Eugenio, Rome, Italy.

Purpose: Despite the identification of several baseline prognostic indicators, the outcome of patients with acute myeloid leukemia (AML) is generally heterogeneous. The effects of autologous (AuSCT) or allogeneic stem-cell transplantation (SCT) are still under evaluation. Minimal residual disease (MRD) states may be essential for assigning patients to therapy-dependent risk categories.

Patients And Methods: By multiparametric flow cytometry, we assessed the levels of MRD in 142 patients with AML who achieved complete remission after intensive chemotherapy.

Results: A level of 3.5 x 10(-4) residual leukemia cells (RLCs) after consolidation therapy was established to identify MRD-negative and MRD-positive cases, with 5-year relapse-free survival (RFS) rates of 60% and 16%, respectively (P < .0001) and overall survival (OS) rates of 62% and 23%, respectively (P = .0001). Of patients (n = 77) who underwent a transplantation procedure (56 AuSCT and 21 SCT procedures); 42 patients (55%) were MRD positive (28 patients who underwent AuSCT and 14 patients who underwent SCT) and 35 patients (45%) were MRD negative (28 patients who underwent AuSCT and seven who underwent SCT). MRD-negative patients had a favorable prognosis, with only eight (22%) of 35 patients experiencing relapse, whereas 29 (69%) of 42 MRD-positive patients experienced relapse (P < .0001). In this high-risk group of 42 patients, we observed that 23 (82%) of 28 of those who underwent AuSCT experienced relapse, whereas six (43%) of 14 who underwent SCT experienced relapse (P = .014). Patients who underwent SCT also had a higher likelihood of RFS (47% v 14%).

Conclusion: A threshold of 3.5 x 10(-4) RLCs postconsolidation is critical for predicting disease outcome. MRD-negative patients have a good outcome regardless of the type of transplant they receive. In the MRD-positive group, AuSCT does not improve prognosis and SCT represents the primary option.
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http://dx.doi.org/10.1200/JCO.2007.15.9814DOI Listing
October 2008

Evaluation of the prognostic relevance of L-selectin and ICAM1 expression in myelodysplastic syndromes.

Eur J Haematol 2008 Feb 17;80(2):107-14. Epub 2007 Nov 17.

Department of Biopatologia e Diagnostica per Immagini, Policlinico Tor Vergata and Ospedale S.Eugenio, Rome, Italy.

Objectives: An aberrant pattern of expression of L-selectin and intercellular adhesion molecule 1 (ICAM1) may characterise CD34+ blast cells in myelodysplastic syndromes (MDS) and secondary acute myeloid leukaemia (sAML).

Methods: In a three-colour flow cytometric assay, we evaluated the expression of L-selectin and ICAM1 on CD34+ blast cells from the bone marrow (BM) of 66 MDS patients; for the purpose of comparison CD34+ blast cells of 18 sAML and CD34+ stem cells of 17 normal donors were also analysed.

Results: The ratio of L-selectin/ICAM1 expression was identified as a parameter correlated with the percentage of BM blast infiltration and the time to leukaemic progression among MDS patients. In fact, the values of L-selectin/ICAM1 ratio were inversely correlated with the BM blast infiltration (r = -0.34, P = 0.004). Furthermore, MDS patients with a baseline ratio <1 had a higher leukaemic progression rate (41% vs. 19%, P = 0.008); the actuarial risk of disease progression for this subgroup of MDS patients was also higher (64% vs. 11% at 2 yr, P = 0.002). Furthermore, in two patients a decrease of the ratio was observed when overt leukaemic transformation occurred; conversely, restoration of a normal ratio was observed in two patients after a chemotherapy-induced remission.

Conclusion: (i) L-selectin is defective in the stem cell compartment of MDS and sAML, whereas ICAM1 is overexpressed; (ii) the ratio of their expression has a prognostic role; and (iii) a ratio <1 significantly predicts progression to overt leukaemia in MDS patients.
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http://dx.doi.org/10.1111/j.1600-0609.2007.00986.xDOI Listing
February 2008

Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow.

Haematologica 2007 May;92(5):605-11

Dept. of Hematology, Policlinico Tor Vergata and Ospedale S.Eugenio, Rome, Italy.

Background And Objectives: To date, bone marrow (BM) is the most common source of cells to use in order to assess minimal residual disease (MRD) in acute myeloid leukemia (AML). In the present study, we investigated whether peripheral blood (PB) could be an alternative source of cells for monitoring MRD in AML.

Design And Methods: Fifty patients with AML were monitored for MRD after the achievement of complete remission. Using multiparametric flow cytometry we compared the levels of MRD in 50 and 48 pairs of BM and PB after induction and consolidation, respectively.

Results: After induction and consolidation therapy, the findings in BM and PB were significantly concordant (r=0.86 and 0.82, respectively, p<0.001 for both comparisons). The cut-off value of residual leukemic cells in PB which correlated with outcome was 1.5x10 (-4). Thirty-three of 43 (77%) patients with >1.5x10 (-4)residual leukemic cells in PB after induction had a relapse, whereas the seven patients with lower levels did not (p=0.0002). After consolidation, 38 patients had a level of MRD >1.5x10 (-4)and 31 (82%) had a relapse; nine out of the remaining ten patients, whose levels of MRD were below 1.5x10 (-4), are still relapse-free (p=0.00006). In multivariate analysis, PB MRD status at the end of consolidation was found to have a significant effect on relapse-free survival (p=0.036).

Interpretation And Conclusions: These preliminary results indicate that: (i) PB evaluation can integrate BM assessment for MRD detection in patients with AML; (ii) PB MRD status at the end of consolidation therapy may provide useful prognostic information.
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http://dx.doi.org/10.3324/haematol.10432DOI Listing
May 2007

Elderly patients with Ph+ chronic myelogenous leukemia (CML): results of imatinib mesylate treatment.

Leuk Res 2005 Mar;29(3):287-91

Dipartimento di Biotecnologie Umane ed Ematologia, Università "La Sapienza" di Roma, Via Benevento 6-00161, Rome, Italy.

Thirty-five patients with Ph+ CML aged more than 60 years were treated with imatinib. Twenty-four patients (group A) were in late chronic phase (CP) and eleven patients (group B) were in accelerated/blastic phase (AP/BP). In group A, complete haematological response (CHR) was achieved by all patients; seventeen patients (70.8%) attained a complete cytogenetic response (CCR), one (4.1%) attained a partial CR, one (4.1%) a minor CR (Ph+ 70%) and five (21%) were resistant (Ph+ 100%), toxicity was mild: seven patients had a transient cytopenia, three a skin reaction, one a moderate oedema and one muscular pain. After a median follow-up of 15 months, 1 patient died in progression and 23 patients are alive (2 in BP and 21 in persisting response). In group B, one patient died after 3 months in aplastic phase from sepsis, three patients were resistant and seven patients (63.7%) achieved CHR; of these, four obtained CCR. After a median follow-up of 17 months, 4 patients have died from progressive disease, 6 are alive; 1 in AP and 5 in CHR (4 of them being in CCR). Present data indicate that imatinib is safe also in elderly with clinical results as good as in younger patients.
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http://dx.doi.org/10.1016/j.leukres.2004.08.002DOI Listing
March 2005

Clinical features of prognostic significance in myelodysplastic patients with normal karyotype at high risk of transformation.

Leuk Res 2005 Jan;29(1):33-9

Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Via Benevento 6, 00161 Rome, Italy.

The International Prognostic Scoring System (IPSS) for myelodysplastic syndromes (MDS) has defined patients with a normal karyotype as a good risk cytogenetic subgroup, but nevertheless a fraction of these patients has a poor outcome similar to that of high risk patients. We retrospectively analysed our series of myelodysplastic patients with normal karyotype observed in a period of 11 years, with the aim of identifying clinical features of possible prognostic significance within this subgroup of patients. Multivariate analysis showed that among clinical scoring systems, the Bournemouth score appears the best prognostic indicator for risk of leukemic transformation, and platelet count <100 x 10(9)/l(-1), presence of haemorrhagic symptoms at time of diagnosis and morphologic FAB classification are the main prognostic factors for prediction of survival. In the absence of genetic abnormalities as detected by conventional cytogenetics or even the more sensitive molecular techniques in MDS, clinical variables could be of help in identifying patients with different prognosis, suitable for risk adapted therapeutic strategies.
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http://dx.doi.org/10.1016/j.leukres.2004.05.010DOI Listing
January 2005

Paroxysmal cold haemoglobinuria as a tardive complication of idiopathic myelofibrosis.

Eur J Haematol 2004 Oct;73(4):304-6

Department of Cellular Biotechnology and Hematology, University La Sapienza, Rome, Italy.

Paroxysmal cold haemoglobinuria (PCH) is an autoimmune haemolytic anaemia caused by the Donath-Landsteiner antibody. It is classically described in association with chronic syphilis or after acute viral infections. We describe the first case of PCH presented as a late manifestation of advanced myelofibrosis associated with antiphospholipid syndrome, that promptly responded to high dosage of prednisone.
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http://dx.doi.org/10.1111/j.1600-0609.2004.00301.xDOI Listing
October 2004