Publications by authors named "Riccardo Varaldo"

34 Publications

Menstrual cycle resumption and female fertility after autologous hematopoietic stem cell transplantation for multiple sclerosis.

Mult Scler 2021 Mar 12:13524585211000616. Epub 2021 Mar 12.

Physiopathology of Human Reproduction Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Data on fertility after autologous hematopoietic stem cell transplantation (aHSCT) in women with multiple sclerosis (MS) are inconclusive. This study aims to report on post-aHSCT menstrual resumption in a multi-center MS-women cohort. Out of 43 women, 30 (70%) recovered menses after a mean time of 6.8 months. Older age (odds ratio (OR) = 0.5, < 0.0001) and previous pulsed cyclophosphamide (OR = 0.44, = 0.005) were independently associated with a reduced menstrual recovery probability. Conditioning regimens' intensity resulted not associated with post-procedure amenorrhea. Our results highlight younger age as significantly associated with menses recovery; proper fertility counseling for MS women candidated to aHSCT both prior- and post-transplantation is therefore warranted.
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http://dx.doi.org/10.1177/13524585211000616DOI Listing
March 2021

Second haploidentical stem cell transplantation for primary graft failure.

Bone Marrow Transplant 2020 Dec 16. Epub 2020 Dec 16.

IRCCS Policlinico San Martino IST, Genova, Italy.

We report the outcome of 19 patients who experienced primary graft failure (PrGF) after a haploidentical (HAPLO), unmanipulated bone marrow transplant. The median age of patients was 52 years; the conditioning regimen of the first HAPLO transplant was either full dose total body irradiation (TBI) or fludarabine, busulfan, and thiotepa (TBF); PTCY was given to all patients together with cyclosporine and mycophenolate. All 19 patients with PrGF received a second HAPLO graft, at a median interval of 42 days (34-82) after HSCT, using the Baltimore protocol and G-CSF mobilized PB from the same (n = 13) or another HAPLO family donor (n = 6). GvHD prophylaxis was again PTCY-based; 14/19 patients had trilineage recovery (74%) and 1-year survival was 66%. Engraftment at second HAPLO was seen in 7/8 patient with, and in 5/7 patients without donor-specific antibodies (DSA). In a multivariate logistic regression analysis on the original group of 503 patients, there was a trend for a reduced dose of busulfan, to increase the risk of PrGF (p = 0.1). In conclusion, patients with PrGF following a HAPLO transplant, can be rescued with a second early HAPLO transplant, using the same or a different donor.
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http://dx.doi.org/10.1038/s41409-020-01183-9DOI Listing
December 2020

The new small tyrosine kinase inhibitor ARQ531 targets acute myeloid leukemia cells by disrupting multiple tumor-addicted programs.

Haematologica 2020 10 1;105(10):2420-2431. Epub 2020 Oct 1.

University of Genoa, DiMI; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Tyrosine kinases have been implicated in promoting tumorigenesis of several human cancers. Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers. Here, we characterize a new multiple kinase inhibitor, ARQ531, and evaluate its mechanism of action in preclinical models of acute myeloid leukemia. Treatment with ARQ531, by producing global signaling pathway deregulation, resulted in impaired cell cycle progression and survival in a large panel of leukemia cell lines and patient-derived tumor cells, regardless of the specific genetic background and/or the presence of bone marrow stromal cells. RNA-seq analysis revealed that ARQ531 constrained tumor cell proliferation and survival through Bruton's tyrosine kinase and transcriptional program dysregulation, with proteasome-mediated MYB degradation and depletion of short-lived proteins that are crucial for tumor growth and survival, including ERK, MYC and MCL1. Finally, ARQ531 treatment was effective in a patient-derived leukemia mouse model with significant impairment of tumor progression and survival, at tolerated doses. These data justify the clinical development of ARQ531 as a promising targeted agent for the treatment of patients with acute myeloid leukemia.
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http://dx.doi.org/10.3324/haematol.2019.224956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556675PMC
October 2020

Autologous hematopoietic stem cell transplantation following alemtuzumab therapy in aggressive multiple sclerosis: A report of three cases.

Mult Scler 2020 Aug 25:1352458520914818. Epub 2020 Aug 25.

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa and Ospedale Policlinico San Martino IRCCS, Genoa, Italy.

The management of multiple sclerosis patients with persistent disease activity under alemtuzumab treatment is not established yet. Concerns have been raised on the safety of autologous haematopoietic stem cell transplantation (aHSCT) after alemtuzumab treatment because of the risk of serious infectious adverse events. We report short-term safety and efficacy data from three patients treated with aHSCT following alemtuzumab treatment. Early adverse events were consistent with expected transplant toxicities. All patients were free of disease activity at the last follow-up. Our data suggest that aHSCT can be considered as a rescue treatment strategy for MS patients with persistent disease activity during alemtuzumab treatment.
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http://dx.doi.org/10.1177/1352458520914818DOI Listing
August 2020

Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody-Begelomab.

Bone Marrow Transplant 2020 08 13;55(8):1580-1587. Epub 2020 Mar 13.

Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Roma, Italy.

We have treated 69 patients with steroid refractory acute graft versus host disease (SR-aGvHD), with an anti-CD26 monoclonal antibody (Begelomab): 28 patients in two prospective studies (EudraCT No. 2007-005809-21; EudraCT No. 2012-001353-19), and 41 patients on a compassionate use study. The median age of patients was 42 and 44 years; the severity of GvHD was as follows: grade II in 8 patients, grade III in 33, and grade IV in 28 patients. There were no adverse events directly attributable to the antibody. Day 28 response was 75% in the prospective studies and 61% in the compassionate use patients, with complete response rates of 11 and 12%. Response for grade III GvHD was 83 and 73% in the two groups; response in grade IV GvHD was 66 and 56% in the two groups. Non relapse mortality (NRM) at 6 months was 28 and 38%. Overall there were 64, 56, 68% responses for skin, liver, and gut stage 3-4 GvHD. The overall survival at 1 year was 50% for the prospective studies and 33% for the compassionate use patients. In conclusion, Begelomab induces over 60% responses in SR-aGvHD, including patients with severe gut and liver GvHD, having failed one or more lines of treatment.
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http://dx.doi.org/10.1038/s41409-020-0855-zDOI Listing
August 2020

Hepatitis E Virus Infection in an Italian Cohort of Hematopoietic Stem Cell Transplantation Recipients: Seroprevalence and Infection.

Biol Blood Marrow Transplant 2020 07 19;26(7):1355-1362. Epub 2020 Mar 19.

Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy; Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address:

Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion.
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http://dx.doi.org/10.1016/j.bbmt.2020.03.012DOI Listing
July 2020

Haploidentical Transplants with Post-Transplant Cyclophosphamide for Relapsed or Refractory Hodgkin Lymphoma: The Role of Comorbidity Index and Pretransplant Positron Emission Tomography.

Biol Blood Marrow Transplant 2018 12 21;24(12):2501-2508. Epub 2018 Jul 21.

Division of Haematology and Bone Marrow Transplantation, Policlinico San Martino, IRCCS Ospedale Policlinico San Martino, Genoa, Italy per l'Oncologia, Genoa, Italy.

Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P = .03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P = .02; and HR, 4.2; 95% CI, 1.7 to 9.9; P = .001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P = .005, HR, 3.8; 95% CI, 1.5 to 9.7; P = .005; and 3.2; 95% CI, 1.3 to 7.9; P = .01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.
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http://dx.doi.org/10.1016/j.bbmt.2018.07.025DOI Listing
December 2018

De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period.

Biol Blood Marrow Transplant 2018 08 22;24(8):1721-1726. Epub 2018 Mar 22.

Division of Infectious Diseases, Department of Health Science (DISSAL), Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy. Electronic address:

To investigate rates and outcomes of antibiotic de-escalation during pre-engraftment neutropenia in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March 2014 were analyzed. De-escalation was defined as narrowing the spectrum of antibiotic treatment either within (early) or after 96 hours (late) from starting antibiotics. Discontinuation, considered a form of de-escalation, was defined as stopping antibiotics before engraftment. De-escalation failure was defined as restarting/escalating antibiotics within 96 hours after de-escalation. Predictors of de-escalation were analyzed. Among 102 patients who started antibiotics and were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n = 58), whereas 34 (33%) received combination therapy (mainly meropenem plus glycopeptide, n = 24). Median duration of neutropenia was 17 days. Bloodstream infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate was 25.5% (n = 26) and mostly consisted of reducing the spectrum of β-lactams (n = 11, 42%). In comparison with theoretical scenario of continuing therapy until engraftment, the median savings in terms of antibiotic days were 10 for meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n = 31) and failure rate 19% (6/31). The rate of de-escalation any time before engraftment was 55.9% (n = 57), including discontinuation in 33 patients (32%). Death at day 60 after HSCT occurred in 3 patients who never underwent de-escalation. Acute myeloid disease and BSIs were independent predictors of early de-escalation. De-escalation, including discontinuation, is feasible and safe in pre-engraftment neutropenia after allogeneic HSCT.
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http://dx.doi.org/10.1016/j.bbmt.2018.03.018DOI Listing
August 2018

Impact of HLA Disparity in Haploidentical Bone Marrow Transplantation Followed by High-Dose Cyclophosphamide.

Biol Blood Marrow Transplant 2018 01 9;24(1):119-126. Epub 2017 Oct 9.

U.O. Ematologia, Ospedale Policlinico San Martino, Genova, Italy.

We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.
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http://dx.doi.org/10.1016/j.bbmt.2017.10.002DOI Listing
January 2018

Pre-Engraftment Bloodstream Infections after Allogeneic Hematopoietic Cell Transplantation: Impact of T Cell-Replete Transplantation from a Haploidentical Donor.

Biol Blood Marrow Transplant 2018 01 30;24(1):109-118. Epub 2017 Aug 30.

Division of Hematology and Bone Marrow Transplantation, San Martino Hospital, Genoa, Italy.

Bloodstream infections (BSIs) are frequent and important infectious complications after hematopoietic cell transplantation (HCT). The aim of this study was to analyze the incidence, risk factors, and outcome of pre-engraftment BSIs after allogeneic HCT. We retrospectively analyzed data from 553 consecutive patients who underwent HCT between 2010 and 2016. Sixty percent of the patients received T cell-replete unmanipulated haploidentical bone marrow with high-dose post-transplantation cyclophosphamide. The BSI rate was 30%; among isolated 213 pathogens, 54% were Gram-positive, 43% were Gram-negative, and 3% were fungi. Independent risk factors for pre-engraftment BSI were transplantation from a haploidentical donor or from cord blood (P < .001), active disease (P = .002), age (P = .04), and myeloproliferative disorders or aplastic anemia (P < .001). Transplantation from a haploidentical donor was an independent risk factor for both Gram-positive and Gram-negative BSI. The 7-day mortality after any BSI was 5% (9 of 178), and in multivariate analysis, BSI etiology was the sole risk factor, with increased mortality in carbapenem-resistant Gram-negative BSI (P < .001). Nonrelapse mortality at day +60 after HCT was 3.8% (21 of 553); independent predictors were active disease (P = .045), year of HCT (P = .027), nonengraftment (P = .001), and pre-engraftment BSI (P < .001), with significantly higher risk in BSI due to Gram-negative pathogens compared with Gram-positive pathogens, and BSI due to carbapenem-resistant Gram-negative pathogens compared with susceptible pathogens. Pre-engraftment BSI is a frequent complication after HCT from a haploidentical donor or cord blood. Because the negative impact of pre-engraftment BSI on 60-day nonrelapse mortality was caused mainly by carbapenem-resistant Gram-negative pathogens, particular attention should be given to appropriate empiric therapy and management of patients at high risk for Gram-negative BSI.
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http://dx.doi.org/10.1016/j.bbmt.2017.08.024DOI Listing
January 2018

Good tolerability of high dose colistin-based therapy in patients with haematological malignancies.

Infection 2017 Aug 28;45(4):505-511. Epub 2017 Mar 28.

Division of Infectious Diseases, Department of Health Sciences (DISSAL), IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.

Purpose: Colistin is usually the only drug fully active against multi-drug resistant Gram-negative bacteria, but its nephrotoxicity might limit its use. Recent pharmacokinetic/pharmacodynamic data suggest that high dose of colistin, preceded by a loading dose, are needed to maximize its antibacterial effect. The aim of this study was to determine the safety of high doses colistin, in haematology population.

Methods: A retrospective review of haematology patients who received high dose colistin-based therapy in years 2011-2016 was performed. Nephrotoxicity was assessed using RIFLE criteria.

Results: Thirty patients who received 38 courses of colistin were included in the study. Colistin was always administered together with other antibiotics. Colistin was well tolerated, with one case of neurological toxicity and one of cutaneous reaction. There were 22 (58%) treatment cycles without any nephrotoxicity, even though during 16 of these cycles other nephrotoxic drugs were administered. Severe (injury or failure) renal toxicity occurred during 6 (16%) treatment courses, requiring colistin discontinuation in 2 patients and colistin dose reduction in 1. Poorer renal function at baseline and younger age were the only variables associated with increased renal toxicity (p = 0.011 and p = 0.031, respectively). Overall mortality was 18% (7/38) and 29% (11/38) at 7 and 30 days after the treatment onset.

Conclusions: In adult haematology population, high dose colistin therapy is safe and efficacious, despite high frequency of concomitant nephrotoxic treatment.
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http://dx.doi.org/10.1007/s15010-017-1010-7DOI Listing
August 2017

Wilms Tumor 1 Expression and Pre-emptive Immunotherapy in Patients with Acute Myeloid Leukemia Undergoing an Allogeneic Hemopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2016 07 10;22(7):1242-1246. Epub 2016 Mar 10.

Cattedra di Ematologia, Universita' Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli, Roma, Italy. Electronic address:

Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1.
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http://dx.doi.org/10.1016/j.bbmt.2016.03.005DOI Listing
July 2016

Improved Outcome of Alternative Donor Transplantations in Patients with Myelofibrosis: From Unrelated to Haploidentical Family Donors.

Biol Blood Marrow Transplant 2016 Feb 9;22(2):324-329. Epub 2015 Oct 9.

Istituto di Ematologia, Universita' Cattolica del Sacro Cuore, Fondazione Policlinico A Gemelli, Roma, Italy. Electronic address:

This is a retrospective analysis of 95 patients with myelofibrosis who were allografted between 2001 and 2014. The aims of the study were to assess whether the outcome of alternative donor grafts has improved with time and how this compares with the outcome of identical sibling grafts. Patients were studied in 2 time intervals: 2000 to 2010 (n = 58) and 2011 to 2014 (n = 37). The Dynamic International Prognostic Scoring System score was comparable in the 2 time periods, but differences in the most recent group included older age (58 versus 53 years, P = .004), more family haploidentical donors (54% versus 5%, P < .0001), and the introduction of the thiotepa-fludarabine-busulfan conditioning regimen (70% of patients versus 2%, P < .0001). Acute and chronic graft-versus-host disease were comparable in the 2 time periods. The 3-year transplantation-related mortality (TRM) in the 2011 to 2014 period versus the 2000 to 2010 period is 16% versus 32% (P = .10), the relapse rate 16% versus 40% (P = .06), and actuarial survival 70% versus 39% (P = .08). Improved survival was most pronounced in alternative donor grafts (69% versus 21%, P = .02), compared with matched sibling grafts (72% versus 45%, P = .40). In conclusion, the outcome of allografts in patients with myelofibrosis has improved in recent years because of a reduction of both TRM and relapse. Improvement is most significant in alternative donor transplantations, with modifications in donor type and conditioning regimen.
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http://dx.doi.org/10.1016/j.bbmt.2015.09.028DOI Listing
February 2016

Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia.

Ann Hematol 2014 Dec 4;93(12):2011-8. Epub 2014 Jul 4.

Division of Clinical Hematology and Division of Hematology and Hematopoietic Stem Cell Transplantation, IRCCS S Martino-IST, Viale Benedetto XV, N 6, 16132, Genova, Italy.

Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoietic stem cell transplantation (HSCT), when clinically indicated, between May 2000 and January 2013. Forty-one patients had acute myeloid leukemia (AML), and 38 had acute lymphoblastic leukemia (ALL). Two patients with myeloid blast crises of CML and three with lymphoid blast crises were included in the AML and ALL subgroups, respectively. Median age was 48 years (range 13-77). FLAD was well tolerated with negligible, nonhematological toxicity. Six patients (7.5 %) died before response evaluation. Forty-seven patients achieved hematologic complete response (CR). Complete remission rate was 53 and 65 % among AML and ALL patients, respectively. No CR was recorded among 11 refractory AML patients. Twenty-four patients (30 %) underwent HSCT. Nine patients received stem cells from an HLA identical sibling, and 15 from an alternative donor (3 unrelated matched, 12 haploidentical sibling). Median overall survival in AML and ALL patients receiving FLAD therapy was 9 and 8 months, respectively. A 5-year projected OS for patients receiving the whole program (FLAD + HSCT) was 24 % for AML patients (median survival 43 months), 28 % for ALL patients treated in relapse (median survival 15 months), and 0 % for ALL patients treated for refractory disease. In this paper, we show that FLAD seems to be an effective bridge therapy to HSCT for a part of poor prognosis acute leukemia patients. However, prospective studies are needed to confirm our results.
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http://dx.doi.org/10.1007/s00277-014-2143-8DOI Listing
December 2014

Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts.

Biol Blood Marrow Transplant 2014 Oct 5;20(10):1573-9. Epub 2014 Jun 5.

Division of Hematology and Marrow Transplantation, Istituto Ricerca Carattere Scientifico (IRCCS), San Martino Istituto Tumori (IST), Genova, Italy. Electronic address:

We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor.
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http://dx.doi.org/10.1016/j.bbmt.2014.05.029DOI Listing
October 2014

CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation.

Biol Blood Marrow Transplant 2014 Sep 24;20(9):1440-3. Epub 2014 May 24.

Divisione di Ematologia e Trapianto di Midollo Osseo, IRCCS AOU San Martino-IST, Genova, Italy. Electronic address:

Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated.
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http://dx.doi.org/10.1016/j.bbmt.2014.05.016DOI Listing
September 2014

Epidemiology of viral respiratory tract infections in an outpatient haematology facility.

Ann Hematol 2014 Apr 6;93(4):669-76. Epub 2013 Oct 6.

Division of Infectious Diseases, San Martino Hospital and University of Genoa, Largo R. Benzi, 10-16132, Genoa, Italy,

Viral respiratory tract infections (VRTI) are an important cause of morbidity and mortality in haematology patients, particularly after haematopoietic stem cell transplantation (HSCT). The incidence, clinical presentation and outcome of symptomatic and asymptomatic VRTI in HSCT outpatient unit were prospectively evaluated during a single influenza season (January-March 2011). Pharyngeal swabs were performed at the first visit and if new symptoms were present. Molecular multiplex assay for 12 respiratory viruses was performed by the regional reference laboratory. Among 264 swabs from 193 outpatients, 58 (22 %) resulted positive for 61 viruses (influenza, n = 20; respiratory syncytial virus [RSV], n = 21; rhinovirus, n = 12; coronavirus, n = 4; adenovirus, n = 3; parainfluenza, n = 1). VRTI were detected more frequently in the presence of symptoms than in asymptomatic patients: 49 out of 162 (30 %) vs. 9 out of 102 (9 %), p < 0.001. Influenza-like illness syndrome (ILI) was significantly associated with a VRTI if compared to other presentations (42 %), while the European Centre for Disease Prevention and Control definition was not (30 %). Positive predictive value (PPV) of ILI for influenza was 17 %. Influenza and RSV peak periods were contemporary. Influenza prophylaxis was given to 25 patients following exposure. Low rate of progression from upper to lower respiratory tract infection (approximately 5 % for influenza and RSV), no nosocomial epidemics and no VRTI-related deaths were observed. VRTI are very frequent in high-risk haematology outpatients, but symptoms are aspecific and PPV of ILI is low. Symptoms of influenza and RSV overlap. Thus, microbiological diagnosis and contact preventive measures are crucial. Rather than universal influenza prophylaxis, prompt diagnosis and treatment of only documented infections could be pursued.
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http://dx.doi.org/10.1007/s00277-013-1912-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079995PMC
April 2014

Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of WT1 expression.

Br J Haematol 2013 Feb 7;160(4):503-9. Epub 2013 Jan 7.

Divisione Ematologia e Trapianto di Midollo, IRCCS San Martino-IST, Genova, Italy.

We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.
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http://dx.doi.org/10.1111/bjh.12181DOI Listing
February 2013

Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning.

Biol Blood Marrow Transplant 2013 Jan 29;19(1):117-22. Epub 2012 Aug 29.

Divisione Ematologia e Trapianto di Midollo, IRCCS San Martino, Genova, Italy.

Fifty patients with high-risk hematologic malignancies, underwent an unmanipulated haploidentical bone marrow transplantation (BMT), followed by posttransplantation high-dose cyclophosphamide (PT-CY): the myeloablative (MA) conditioning consisted of thiotepa, busulfan, fludarabine (n = 35), or total body irradiation (TBI), fludarabine (n = 15). The median age was 42 years (range, 18-66 years); 23 patients were in remission, 27 had active disease, and 10 patients were receiving a second allograft. Graft-versus-host disease (GVHD) prophylaxis consisted in PT-CY on day +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). Three patients died before engraftment, and 2 patients had autologous recovery: 45 patients (90%) had full-donor chimerism on day +30. The median day for neutrophil engraftment was day +18 (range, 13-30 days). The cumulative incidence of grade II-III acute GVHD (aGVHD) was 12%, and of moderate chronic GVHD (cGVHD) 10%. With a median follow-up for surviving patients of 333 days (range, 149-623 days), the cumulative incidence of transplantation-related mortality (TRM) was 18%, and the rate of relapse was 26%. The actuarial 22-month disease-free survival (DFS) rate was 68% for patients in remission and 37% for patients with active disease (P < .001). Causes of death were pneumonia (n = 3), hemorrhage (n = 3), sepsis (n = 3), and relapse (n = 7). In conclusion, an MA conditioning regimen followed by haploidentical BMT with PT-CY results in a low risk of aGVHD and cGVHD and encouraging rates of TRM and DFS.
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http://dx.doi.org/10.1016/j.bbmt.2012.08.014DOI Listing
January 2013

CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus.

Biol Blood Marrow Transplant 2012 Jan 27;18(1):92-9. Epub 2011 May 27.

Division of Infectious Diseases, San Martino University Hospital, Genoa, Italy.

Cytomegalovirus (CMV) infection and disease are important complications after hematopoietic stem cell transplant, particularly after transplant from alternative donors. Allogeneic cord blood transplantation (CBT) is being increasingly used, but immune recovery may be delayed. The aim of this study was to compare CMV infection in CBT with transplants from unrelated or mismatched related donors, from now on defined as alternative donors. A total of 165 consecutive transplants were divided in 2 groups: (1) alternative donors transplants (n = 85) and (2) CBT recipients (n = 80). Donor and recipient (D/R) CMV serostatus were recorded. The incidence of CMV infection, its severity, timing, and outcome were compared. Median follow-up was 257 days (1-1328). CMV infection was monitored by CMV antigenemia and expressed as CMV Ag positive cell/2 × 10(5) polymorphonuclear blood cells. There was a trend toward a higher cumulative incidence of CMV infection among CBT than alternative donor transplant recipients (64% vs 51%, P = .12). The median time to CMV reactivation was 35 days, and was comparable in the 2 groups (P = .8). The maximum number of CMV-positive cells was similar in the 2 groups (11 versus 16, P = .2). The time interval between the first and the last positive CMV antigenemia was almost 4 times longer in CBT compared with alternative donor transplants (109 vs 29 days, respectively, P = .008). The incidence of late CMV infection was also higher in CBT (62% vs 24%, P < .001). The incidence of early and late CMV infection in CBT was similar to D-/R+ alternative transplants, and higher than in D+/R+ alternative transplants: early infection, 72% in CBT versus 69% in D-/R+ alternative versus 55% in D+/R+ alternative (P = .21); and late infection, 67% in CBT versus 60% in D-/R+ alternative versus 7% in D+/R+ alternative (P < .001). Transplant-related mortality and overall survival were similar between the groups: 34% versus 36% (P = .6) and 54% versus 46% (P = .3) for alternative transplant and CBT, respectively. Longer duration and higher incidence of late CMV infection was seen in CBT patients, when compared with alternative donor transplants, whereas no difference in mortality was observed. The duration and incidence of late CMV infection were similar when D-/R+ CBT were compared with D-/R+ alternative donor transplants.
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http://dx.doi.org/10.1016/j.bbmt.2011.05.015DOI Listing
January 2012

Rituximab treatment for Epstein-Barr virus DNAemia after alternative-donor hematopoietic stem cell transplantation.

Biol Blood Marrow Transplant 2011 Jun 13;17(6):901-7. Epub 2010 Oct 13.

Division of Hematology and Bone Marrow Transplant, Ospedale San Martino, Genova, Italy.

We report 55 patients undergoing an alternative-donor hematopoietic stem cell transplantation (HSCT) who developed Epstein-Barr virus (EBV) DNAemia, with >1000 EBV copies/10(5) peripheral blood mononuclear cells (PBMCs), and were treated with rituximab (375 mg/m(2)). The median patient age was 47 years (range, 20-65 years), and graft sources were mismatched family members (n = 4), unrelated donors (n = 46), and unrelated cord blood (n = 5). The conditioning regimen included antithymocyte globulin (ATG) in all patients. The median time to development of EBV DNAemia was day 27 post-HSCT (range, day 5 to day 242), with a median of 60 EBV copies/10(5) PBMCs (range, 1-5770 copies/10(5) PBMCs). The number of EBV copies was reduced to <1000/10(5) PBMCs on day +7 after initiation of rituximab therapy in 51% of the patients, on day +14 in 73% of the patients, and on +21 in 92% of the patients. Overall, 50 of 55 patients (91%) cleared EBV after one dose (n = 25) or more than one dose (n = 25) of rituximab. Factors predicting transplantation-related mortality (TRM) in multivariate analysis were a reduction to <1000 EBV copies/10(5) PBMCs by day +7 of treatment (relative risk [RR], 0.2; P = .01) and disease phase in remission (RR, 0.3; P = .05). TRM was 23% in the 40 patients with none or one of the negative predictors and 60% in the 15 patients with both negative predictors (P = .001). Of these latter 15 patients, 3 developed clinical posttransplantation lymphoproliferative disorder (PTLD). All 3 of these patients had a high EBV load on day +7 of rituximab therapy. This study confirms the effectiveness of rituximab in controlling EBV DNAemia in patients undergoing allogeneic HSCT. Patients with increasing EBV copies despite rituximab therapy are at high risk for EBV PTLD and may be considered for alternative therapies.
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http://dx.doi.org/10.1016/j.bbmt.2010.10.003DOI Listing
June 2011

The intra-bone marrow injection of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic diseases.

Best Pract Res Clin Haematol 2010 Jun;23(2):237-44

Centro Cellule Staminali e Terapia Cellulare, Ospedale San Martino, Genova, Italy.

Cord blood transplant (CBT) in adult patients is scarcely utilized because of the risk of graft failure or very delayed platelet recovery. To improve the capacity and the speed to engraft, we have developed an intra-bone (IB) cord blood transplant technique. 75 patients with hematological malignancies, categorized by disease phase as early (18%), intermediate (20%) and advanced (62%), were transplanted. The median cell dose (TNC) infused was: 2.6 (1.35-5.4)×10(7)/kg; the HLA disparity was: 12 cases=5/6, 62 cases=4/6 and 1 case=3/6 matched antigens. 72/75 patients engrafted (96%); median day of recovery of neutrophils (PMN) >500×10(9)/L and platelets (PLT) >20 000×10(9)/L was: 23 (14-44) and 35 (16-70) days respectively. The outcomes at 2 years according to Kaplan-Meier are: OS=46%±5; RI=18%±2; NRM=39%±5. Acute GVHD incidence/severity was: grade 0-I=64%, II=14%, III-IV=0%. The incidence of Chronic GVHD was globally low but in 3 cases was very severe. Intra-bone CBT is associated with high rate of engraftment, early and robust platelet recovery, low incidence of acute GVHD. A very promising aspect is that the relapse rate is low considering the advanced phase of the disease in two/thirds of patients. A suitable CBU was found for nearly every patient searching for a CBU. Therefore, IB CBT extends the possibility to transplant any patient for whom this approach represents the sole possibility of long-term survival.
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http://dx.doi.org/10.1016/j.beha.2010.06.003DOI Listing
June 2010

Seventeen years of experience with ATRA-based therapy for acute promyelocytic leukaemia: long-term follow-up of patients treated at S. Martino Hospital, Genoa.

Oncol Rep 2009 Apr;21(4):1045-52

Department of Haematology, University of Genoa, 16132 Genoa, Italy.

We conducted a long-term follow-up retrospective study on 91 consecutive newly diagnosed acute promyelocytic leukaemia (APL) patients. Induction and consolidation therapy were well-tolerated by most patients. Of the 79 patients who were initially treated with the all-trans retinoic acid (ATRA)-containing regimens, there were 3 haemorrhagic deaths during the first period of therapy (4%) and one in consolidation which was due to infection. Following consolidation, molecular assessment of response was performed on 67 patients, and 66 were found to have achieved cytogenetic and molecular remission (98%). After a median follow-up of 100 months (12-192), 10 of the 75 patients who achieved complete remission (13%) relapsed. Seventy-eight percent of the patients were expected to be alive at 14 years from diagnosis, i.e., 90 and 48% of patients of intermediate-low risk and high risk at presentation, respectively (p=0.0009). Sixty-nine patients were in molecular remission after first-line and/or salvage therapy (74%). To date, 4 patients out of the 91 have undergone salvage allogeneic transplant (4%).
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http://dx.doi.org/10.3892/or_00000322DOI Listing
April 2009

The addition of radiotherapy to chemotherapy does not improve outcome of early stage Hodgkin's lymphoma patients: a retrospective long-term follow-up analysis of a regional Italian experience.

Ann Hematol 2009 Sep 3;88(9):855-61. Epub 2009 Feb 3.

Department of Haematology and Oncology, University of Genova, San Martino Hospital, Viale Benedetto XV, N 6, Genova, Italy.

We retrospectively reviewed 139 stage I-II HL patients who were diagnosed and followed up in an Italian northern region (Liguria) from 1995 to 2007, and who received either chemotherapy (CT) alone (mainly doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) or a combined modality treatment (chemotherapy + radiotherapy, CT + RT). The two therapeutic groups were comparable for clinical and histologic features. Complete remission rate after CT + RT was higher than what was achieved with CT alone (96% vs. 84%, respectively, p = 0.03). Relapse rate (12%) was the same in both groups and disease-free survival curves were comparable (82% and 83%, p = 0.47). The overall survival of the two therapeutic groups is comparable. No second tumors have been reported among patients receiving chemotherapy alone, whereas a second neoplasia has been diagnosed in four patients (in two cases possibly radiotherapy related) in the CT + RT group (5%, p = 0.09) In conclusion, our retrospective study shows that CT + limited RT is an effective and well-tolerated option for early stage Hodgkin's lymphoma, even if the use of RT is associated with a certain risk of developing a second tumor. However, four to six courses of ABVD can lead to similar, optimal, long-term disease control without exposing patients to the risk of a second neoplasia.
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http://dx.doi.org/10.1007/s00277-009-0699-5DOI Listing
September 2009

Treatment of Philadelphia-positive chronic myeloid leukemia with imatinib: importance of a stable molecular response.

Clin Cancer Res 2009 Feb;15(3):1059-63

Department of Hematology/Oncology L. and A. Seràgnoli, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Purpose: The achievement of a major molecular response (MMolR) at 12 months is a surrogate marker of progression-free survival in chronic myeloid leukemia patients treated with imatinib.

Experimental Design: We evaluated the prognostic value of the long-term evolution of the molecular response based on a retrospective analysis of 130 late chronic phase chronic myeloid leukemia patients who achieved a complete cytogenetic response (CCgR) with 400 mg/d imatinib and have now a median follow-up of 72 months (range, 48-77).

Results: In 71 (55%) patients, molecular response was consistently major (stable MMolR); in 19 (15%) patients, molecular response was occasionally less than major (unstable MMolR); in 40 (30%) patients, MMolR was never achieved (never MMolR) during all the course of CCgR. Patients with stable MMolR had a longer CCgR duration and a significantly better progression-free survival compared with patients with absent or unstable MMolR. The achievement of a MMolR, if maintained continuously, conferred a marked long-term stability to the CCgR: patients with a stable MMolR have a significantly lower risk of losing the CCgR than patients with unstable and never MMolR (4% versus 21%, P = 0.03, and 4% versus 33%, P < 0.0001, respectively). Finally, if a MMolR is not maintained consistently, the risk of losing the CCgR is higher but not significantly than if it is never achieved (33% versus 21%, P = 0.5).

Conclusions: These data confirm that achieving a MMolR is prognostically important but point out that the prognostic value of achieving a MMolR is greater if the response is confirmed and stable.
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http://dx.doi.org/10.1158/1078-0432.CCR-08-1195DOI Listing
February 2009

Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up.

Haematologica 2008 Dec 6;93(12):1792-6. Epub 2008 Oct 6.

Institute of Hematology and Medical Oncology L. and A. Seràgnoli, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Background: Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients.

Design And Methods: We conducted a phase II trial of imatinib 600 mg daily in patients with chronic myeloid leukemia in blast crisis. The return to chronic phase was defined as <15% blasts and <30% blasts plus promyelocytes in blood or bone marrow and <20% peripheral basophils. A complete hematologic response required the normalization of platelet and white cell differential counts and absence of extramedullary involvement. Cytogenetic response was assessed by the standard banding technique and rated as usual.

Results: Ninety-two patients were enrolled (20 with lymphoid blast crisis and 72 with myeloid blast crisis). Forty-six patients (50%) returned to chronic phase, and 24 patients (26%) achieved also a complete hematologic response. Sixteen patients (17%) had a cytogenetic response (9 complete, 1 partial, and 6 minor or minimal). The complete cytogenetic response was subsequently lost by all but two patients between 2 and 12 months after first having achieved it: the median duration of complete cytogenetic response was 7 months. All responses were sustained for a minimum of 4 weeks. The median survival of all the patients was 7 months. After a median observation time of 66 months, seven (8%) patients are alive. Three of these patients are on imatinib treatment (1 in complete hematologic remission, 1 in partial cytogenetic response and 1 in complete cytogenetic remission). Three patients are in complete remission after allogeneic stem cell transplantation. One patient is alive in blast crisis, on therapy with a second-generation tyrosine kinase inhibitor.

Conclusions: Imatinib was effective and safe in the short-term treatment of chronic myeloid leukemia in blast crisis, but longer-term outcome was not significantly influenced (ClinicalTrials.gov identifier: NCT00514969).
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http://dx.doi.org/10.3324/haematol.13068DOI Listing
December 2008

Adding low-dose gemtuzumab ozogamicin to fludarabine, Ara-C and idarubicin (MY-FLAI) may improve disease-free and overall survival in elderly patients with non-M3 acute myeloid leukaemia: results of a prospective, pilot, multi-centre trial and comparison with a historical cohort of patients.

Br J Haematol 2007 Jul;138(2):186-95

Department of Haematology and Oncology, University of Genova and S. Martino Hospital, Genova, Italy.

We report the final results of a prospective multi-centre trial testing the combination of chemotherapy (fludarabine, cytosine arabinoside and idarubicin; FLAI) followed by low-dose gemtuzumab ozogamicin (GO), for induction treatment of patients with CD33+ acute myeloid leukaemia (AML). Forty-six consecutive patients were treated: the median age was 66 (range: 60-80) years; the karyotype was unfavourable in 12 patients (26%), intermediate in 33 (71%) and favourable in one (3%). Eleven major infectious complications were recorded. There was one early death. Of the 45 evaluable patients, 24 achieved a complete response (CR; 52%), 66% and 33% in good-intermediate/poor karyotype patients. Median duration of CR was 7 (3-24) months. The cumulative incidence of relapse was 37% with an actuarial 2-year survival of 54%. These results were compared with 47 patients matched for age and karyotype who received FLAI, without GO. The proportion of patients achieving CR was comparable. However, patients with de novo AML receiving GO (n = 26) had a significantly lower risk of relapse at 2 years when compared with patients not receiving GO (n = 35) (40% vs. 80%, P = 0.01) and significantly better overall 2-year survival (40% vs. 14%P = 0.02). Patients with secondary AML had comparable outcome whether or not they received GO. This GO-based induction chemotherapy has a good toxicity profile. In keeping with a recent prospective randomised trial, the addition of GO seems to prolong disease-free survival.
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http://dx.doi.org/10.1111/j.1365-2141.2007.06646.xDOI Listing
July 2007

Molecular analysis of the Imatinib-induced complete cytogenetic response in chronic myelogenous leukemia.

Leuk Lymphoma 2006 Jul;47(7):1348-51

Department of Haematology and Oncology, Azienda Ospedale S.Martino e Cliniche Universitarie Convenzionate, Genova, Italy.

The aim of this study was to elucidate the relationship between clonal and normal haematopoiesis in chronic myelogenous leukemia (CML). Thirteen female patients who reached complete cytogenetic response (CCR) after Imatinib treatment were studied. Although all the study patients exhibited a polyclonal pattern of X inactivation, p210 BCR/ABL transcript remained detectable in all cases by nested RT-PCR. This study also demonstrated the presence of p190 transcript in nine out of 13 study patients. A longer follow-up analysis is needed to clarify the prognostic value of these results. The recent observation that clonal cytogenetic abnormalities may occur in CML patients in polyclonal remission after imatinib suggests that a neoplastic stem cell lacking BCR/ABL rearrangement may acquire further cytogenetic alterations other than Philadelphia chromosome.
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http://dx.doi.org/10.1080/10428190500525607DOI Listing
July 2006

Ifosfamide, epirubicin, etoposide (IEV) and autologous peripheral blood progenitor cell transplant: a feasible and effective salvage treatment for lymphoid malignancies.

Oncol Rep 2005 Oct;14(4):933-40

Department of Haematology, University of Genova, Viale Benedetto XV, N6, 16132 Genova, Italy.

The IEV schedule consisted of epirubicin 100 mg/m2 on day 1, etoposide 150 mg/m2 on days 1-3, and ifosfamide 2.5 g/m2 on days 1-3. Patients who proceeded to haematopoietic stem cell transplants (HDTs) received conditioning therapy with BEAM [for the Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL) groups], or melphalan 100 mg/m2 and mitoxantrone [for the multiple myeloma (MM) patients]. The study consisted of 65 patients with a median age of 53 years: 27 had aggressive NHL, 20 had HL, 7 had indolent NHL, and 11 had MM. Fifty-five patients received IEV for a disease that was refractory to conventional induction regimens, or that was in first or second relapse; 4 patients were treated with IEV while in complete response (CR) after chemotherapy in order to mobilise peripheral blood stem cells (PBSCs). Ninety percent of patients with HL responded to IEV, and 85% achieved CR. Both aggressive and indolent NHLs were less responsive (ORR 50 and 33%, respectively; CRR 41 and 16.5%, respectively). MM patients displayed an intermediate responsiveness (ORR 50% and CRR 30%). IEV was well tolerated in most patients. No life- threatening infections were recorded. PBSC mobilisation was successful in 37 out of 39 patients (95%) and led to the collection of a median of 16, 12, and 13.7 x 10(6) CD34+ cells/kg in patients with HL, NHL, and MM, respectively. All 37 patients underwent an autologous stem cell transplant following a 1 to 2 month interval after the end of IEV. Two patients were submitted to an allogeneic transplant. The median overall survival rate in HL, aggressive NHL, and indolent NHL is 32 (5-60), 16 (2-46), and 14 (4-42) months, respectively. Median EFS is 31 (5-60), 7 (2-46), and 7.5 (4-42) months, respectively. In conclusion, our study confirms that IEV +/- HDT is a well-tolerated and effective salvage treatment for lymphoid malignancies, and that IEV acts as an excellent stem cell mobiliser.
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October 2005