Publications by authors named "Francesco Grimaldi"

22 Publications

  • Page 1 of 1

The role of ponatinib in adult BCR-ABL1 positive acute lymphoblastic leukemia after allogeneic transplantation: a real-life retrospective multicenter study.

Ann Hematol 2021 Mar 28. Epub 2021 Mar 28.

Divisione di Ematologia con Trapianto di midollo osseo - Azienda ospedaliero, universitaria Policlinico Vittorio Emanuele, Catania, Italy.

The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph'+ ALL) patients post-allogeneic transplantation is limited. We retrospectively collected data on 25 Ph'+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of BCR/ABL1, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph'+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered.
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http://dx.doi.org/10.1007/s00277-021-04504-0DOI Listing
March 2021

Lymphocytes, Interleukin 6 and D-dimer Cannot Predict Clinical Outcome in Coronavirus Cancer Patients: LyNC1.20 Study.

Anticancer Res 2021 Jan;41(1):307-316

Breast Unit, Department of Surgical Science, Policlinico Tor Vergata University, Rome, Italy.

Background/aim: Knowledge of Coronavirus 19 (COVID19) pathogenetic mechanisms is necessary to provide new treatment strategies. This study aims to assess how oncological disease impacts on the clinical course of COVID-19 patients.

Patients And Methods: From 1 March to 30 April 2020, 96 COVID-19 patients were classified according to clinical outcome as severe (n=67) and moderate (n=29). Demographic data, medical history, admission lymphocytes, procalcitonin (PCT), c-reactive-protein (CRP), D-dimer, and Interleukin-6 (IL-6) were collected.

Results: A statistically significant association was found between hypertension (p=0.007) and three or more comorbidities with severe outcomes (p=0.034). No statistical differences were found between the severe and moderate groups with regards to the rate of patients with past oncological history. However, no patient allocated in the moderate group had received oncological treatment within 12 months. Higher values of CRP, IL-6, D-Dimer and lower values of lymphocytes were reported in the severe group (p=0.0007, p=0.00386, p=0.041, and p=0.007, respectively). Using binary logistic regression, higher values of CRP (OR=8.861; p=0.012) and PCT were associated with a higher risk of severe outcome (OR=21.075; p=0.008). Within the oncological population, D-Dimer and IL-6 did not confirm their prognostic significance as in the general population (p>0.05).

Conclusion: Specific prognostic factors for oncological patients should be designed for COVID-19 clinical practice.
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http://dx.doi.org/10.21873/anticanres.14777DOI Listing
January 2021

Chest Computed Tomography Scoring in Patients With Novel Coronavirus-infected Pneumonia: Correlation With Clinical and Laboratory Features and Disease Outcome.

In Vivo 2020 Nov-Dec;34(6):3735-3746

Department of Biomedicine and Prevention, Division of Diagnostic Imaging, Tor Vergata University, and Unit of Diagnostic Imaging, Policlinico Tor Vergata, Rome, Italy.

Background/aim: This study investigated the correlation of chest computed tomography (CT), findings, graded using two different scoring methods, with clinical and laboratory features and disease outcome, including a novel clinical predictive score, in patients with novel coronavirus-infected pneumonia (NCIP).

Patients And Methods: In this retrospective, observational study, CT scan of 92 NCIP patients admitted to Policlinico Tor Vergata, were analyzed using a quantitative, computed-based and a semiquantitative, radiologist-assessed scoring system. Correlations of the two radiological scores with clinical and laboratory features, the CALL score, and their association with a composite adverse outcome were assessed.

Results: The two scores correlated significantly with each other (ρ=0.637, p<0.0001) and were independently associated with age, LDH, estimated glomerular filtration rate, diabetes, and with the composite outcome, which occurred in 24 patients.

Conclusion: In NCIP patients, two different radiological scores correlated with each other and with several clinical, laboratory features, and the CALL score. The quantitative score was a better independent predictor of the composite adverse outcome than the semiquantitative score.
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http://dx.doi.org/10.21873/invivo.12223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811662PMC
November 2020

CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program.

Blood Cancer J 2020 10 6;10(10):96. Epub 2020 Oct 6.

IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT.
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http://dx.doi.org/10.1038/s41408-020-00361-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538937PMC
October 2020

The Q-LAMP Method Represents a Valid and Rapid Alternative for the Detection of the Rearrangement in Philadelphia-Positive Leukemias.

Int J Mol Sci 2019 Dec 4;20(24). Epub 2019 Dec 4.

Department of Molecular Medicine and Biotechnology, University Federico II, 80131 Naples, Italy.

Molecular detection of the fusion transcripts is necessary for the genetic confirmation of a chronic myeloid leukemia diagnosis and for the risk classification of acute lymphoblastic leukemia. mRNAs are usually identified using a conventional RT-PCR technique according to the BIOMED-1 method. In this study, we evaluated 122 -positive samples with the Q-LAMP assay to establish if this technology may represent a valid alternative to the qualitative BIOMED-1 PCR technique usually employed for the detection and the discrimination of the common transcripts (p190 and p210 isoforms). We found a 100% concordance rate between the two methods. Specifically, the p190- and p210-positive samples were amplified by Q-LAMP with a median threshold time (Tt) of 26.70 min (range: 24.45-31.80 min) and 20.26 min (range: 15.25-34.57 min), respectively. A median time of 19.63 was observed in samples displaying both (e13a2/e14a2) p210 isoforms. Moreover, the Q-LAMP assay allowed recognition of the e13a2 and e14a2 isoforms (median Tts 18.48 for e13a2 vs. 26.08 min for e14a2; < 0.001). Finally, 20 samples harboring rare isoforms (e1a3, e13a3, e14a3, and e19a2) were correctly identified by the Q-LAMP assay. We conclude that the Q-LAMP assay may represent a faster and valid alternative to the qualitative BIOMED-1 RT-PCR for the diagnosis at -positive leukemias, especially when samples are analyzed in centers with restricted resources and/or limited technical expertise.
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http://dx.doi.org/10.3390/ijms20246106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941015PMC
December 2019

Similar outcomes of alemtuzumab-based hematopoietic cell transplantation for SAA patients older or younger than 50 years.

Blood Adv 2019 10;3(20):3070-3079

Department of Haematological Medicine, King's College Hospital, London, United Kingdom.

Survival after allogeneic hematopoietic cell transplantation (HSCT) for severe aplastic anemia (SAA) among older patients remains poor and associated with increased risk for graft-versus-host disease (GVHD). In this retrospective study of 65 consecutive patients with acquired SAA who were transplanted using fludarabine, low-dose cyclophosphamide, and alemtuzumab (FCC), outcomes of 27 patients aged at least 50 years were compared with those of 38 patients younger than 50 years. The median age of the older cohort was 61 years (range, 51-71 years); 21 (78%) patients were transplanted from unrelated donors (3 of 21 from HLA 9/10 mismatch donors) and 6 from matched sibling donors. One-year GVHD-free, relapse-free survival (GRFS) was comparable to that of patients younger than 50 years (84% vs 94%, respectively; P = .23). Both groups showed low rates of acute (5% vs 4%) and chronic (18% vs 14%) GVHD, with no cases of severe GVHD among matched donor transplants, and similar 1-year transplant-related mortality (14% vs 5.4%, older vs younger; P = .23). HSCT comorbidity index (HTC-CI) scores were similar between the groups, but overall survival with an HCT-CI of at least 3 was lower compared with a score less than 3 (76% vs 98%; P = .005). Median donor T-cell chimerism among older patients was 64% and 60% at 1 and 3 years, respectively, and was similar to that of younger patients. Increased B regulatory cells potentially contributed to low alloreactivity and mutual donor-recipient tolerance in older patients. Effect of comorbidities rather than age alone may be a more important determinant of suitability for FCC HSCT in older patients.
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http://dx.doi.org/10.1182/bloodadvances.2019000480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849949PMC
October 2019

Full donor chimerism without graft-versus-host disease: the key factor for maximum benefit of pre-emptive donor lymphocyte infusions (pDLI).

Bone Marrow Transplant 2020 03 26;55(3):562-569. Epub 2019 Sep 26.

Haematology Department, King's College Hospital, London, UK.

Compared to standard-conditioned regimens, reduced-intensity conditioning and T-cell depletion deliver lower transplant-related mortality and decreased graft-vs-host disease after allogeneic hematopoietic stem-cell transplantation. These advantages may however be mitigated by increased relapse rates and delays in achievement of full donor chimerism (FDC). Pre-emptive donor lymphocyte infusions (pDLI) facilitate the conversion of mixed (MDC) to FDC. However, there is a lack of published data on the risk/benefit analysis of this intervention. We performed a retrospective analysis of 119 patients who received 276 pDLI doses for falling CD3 chimerism, CD3 < 50% or mixed XX/XY karyotype. 71/119(60%) Patients achieved FDC, with only one reverting to MDC. Cumulative incidence (CI) of relapse at 5 years was significantly lower in the FDC group (16.0 vs 41.4%, p < 0.001). Those patients who achieved FDC had improved EFS (p < 0.001) and OS (p < 0.001). Interestingly, patients with FDC who developed DLI-induced graft-vs-host disease (GvHD) showed a similar outcome to those with MDC. The majority of patients who receive pDLI convert to FDC and retain that status. Achievement of FDC after pDLI impacts on survival, and those patients who achieve FDC without GvHD, experience maximum clinical benefit. Strategies to minimise DLI-induced GvHD should be considered to maximise the therapeutic potential of this intervention.
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http://dx.doi.org/10.1038/s41409-019-0695-xDOI Listing
March 2020

Adding hydroxyurea in combination with ruxolitinib improves clinical responses in hyperproliferative forms of myelofibrosis.

Cancer Med 2019 06 17;8(6):2802-2809. Epub 2019 Apr 17.

Department of Medicine and Surgery, Hematology and Hematopoietic Stem Cell Transplant Center, University of Naples Federico II, Naples, Italy.

Ruxolitinib, an orally bioavailable and selective inhibitor of Janus kinase 1 (JAK1) and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea might improve hematological response. This observational multi-center study enrolled 20 adult patients with intermediate- or high-risk primary MF, post- polycythemia vera MF, or postessential thrombocythemia MF with hyperproliferative manifestations of the disease and WBC and/or platelet counts not controlled by ruxolitinib therapy. The patients received treatment with a combination of ruxolitinib and hydroxyurea. A clinical response of any type was obtained in 8 patients (40%) during ruxolitinib monotherapy and in 17 patients (85%) during ruxolitinib-hydroxyurea combination (P = 0.003). After a median duration of 12.4 months of combination therapy, 16/20 patients had a hematological response; 14/17 patients who had started combination therapy to control WBC count and 2/3 who started in order to reduce platelets count. The number of patients requiring ruxolitinib dosage reduction or discontinuations was lower during combination therapy and, at the end of follow-up the median ruxolitinib dose was increased in 50% of patients. In conclusion, the combination of hydroxyurea with ruxolitinib yielded a high clinical response rate and increased ruxolitinib exposure in patients with hyperproliferative forms of MF.
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http://dx.doi.org/10.1002/cam4.2147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558489PMC
June 2019

A Frontline Approach With Peripherally Inserted Versus Centrally Inserted Central Venous Catheters for Remission Induction Chemotherapy Phase of Acute Myeloid Leukemia: A Randomized Comparison.

Clin Lymphoma Myeloma Leuk 2019 04 20;19(4):e184-e194. Epub 2018 Dec 20.

Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy.

Background: The incidence of peripherally inserted central catheter (PICC)-related adverse events has been uncertain in the setting of acute myeloid leukemia (AML) compared with the incidence of centrally inserted central catheter (CICC) adverse events.

Patients And Methods: We conducted a monocentric, randomized trial of patients with previously untreated AML. Of the 93 patients, 46 had received a PICC and 47 had received a CICC as frontline intravascular device. Thereafter, all patients underwent intensive chemotherapy for hematologic remission induction. The primary endpoint was catheter-related (CR)-bloodstream infection (BSI) and venous thrombosis (VT) rate. The secondary endpoints catheter malfunction, catheter removal, and patient overall survival.

Results: The CR-BSI and CR-VT rate in the PICC and CICC groups was 13% and 49%, respectively, with a difference of 36 percentage points (relative risk for CR-BSI or CR-VT, 0.266; P = .0003). The CR-BSI incidence was 1.4 and 7.8 per 1000 catheters daily in the PICC and CICC groups, respectively. Among the CR thromboses, the symptomatic VT rate was 2.1% in the PICC group and 10.6% in the CICC group. In the CICC group, 16 of the 47 patients (34%) had the catheter removed for BSI (n = 5), septic thrombophlebitis (n = 4), VT (n = 2), or malfunction (n = 5) a median of 7 days after insertion. In the PICC group, only 6 of the 46 patients (13%) required catheter removal for VT (n = 2) or malfunction (n = 4). At a median follow-up of 30 days, 6 patients in the CICC group died of CR complications versus none of the patients in the PICC group (P = .012). Using PICCs, the reduction in BSI and symptomatic VT decreased mortality from CR infection and venous thromboembolism. In contrast, the CICC approach led to early catheter removal mostly for difficult-to-treat infectious pathogens.

Conclusion: Our data have confirmed that BSI and symptomatic VT are the major complications affecting frontline central intravascular device-related morbidity in the leukemia setting. The use of a PICC is safer than that of a CICC and maintains the effectiveness for patients with AML undergoing chemotherapy, with an approximate fourfold lower combined risk of infection or thrombosis at 30 days.
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http://dx.doi.org/10.1016/j.clml.2018.12.008DOI Listing
April 2019

Long-term results of suture annuloplasty for degenerative mitral valve disease: a propensity-matched analysis.

J Cardiovasc Med (Hagerstown) 2018 Jan;19(1):22-28

aDepartment of Cardiac SurgerybDepartment of Clinical CardiologycHeart Failure Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.

Aims: Ring annuloplasty is the gold standard of surgical repair in degenerative mitral valve disease. However, prosthetic annuloplasty has some drawbacks and potential hazards. Suture annuloplasty theoretically is able to preserve annular leaflet dynamics and left ventricular performance, but experience is limited. The aim of the study was to review the early and long-term outcome of the posterior double-suture annuloplasty (DSA) technique for degenerative mitral valve repair.

Methods: From January 2002 to December 2008, 400 patients underwent primary mitral valve repair for degenerative disease either with posterior DSA [n = 147 (37%)] or with flexible posterior annuloplasty band [n = 253 (63%)]. Differences in patient characteristics were addressed by propensity-score matching (132 pairs). A composite end-point of mitral valve failure (MVF) was calculated as the incidence of mitral valve regurgitation greater than 2+ or need for mitral valve replacement at follow-up.

Results: After propensity-score matching, the distribution of preoperative variables among matched pairs was, on average, equal. Isolated annuloplasty and leaflet repair techniques were similarly performed in both groups (P = 0.20). In-hospital mortality was comparable between the two study groups (P = 0.48). Predischarge echocardiography showed excellent results regarding valve hemodynamics (P = 0.71). At a mean follow-up of 11 ± 3 years, all-cause mortality (P = 0.12), need for mitral valve replacement (P = 0.49), and cardiac re-hospitalization rate (P = 0.57) resulted comparable between the two groups. Ten-year survival (75 vs. 71%, P = 0.51) and freedom from MVF (92 vs. 84%, P = 0.39) were similar between posterior annuloplasty band and DSA groups.

Conclusion: Suture annuloplasty demonstrated comparable results with posterior flexible band repair and could be a viable option for mitral valve surgery in selected patients, such as in the minimally invasive approach, in endocarditis, and in developing countries.
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http://dx.doi.org/10.2459/JCM.0000000000000608DOI Listing
January 2018

Acute immune toxicity during anti-thymocyte globulin: That's CARPA!

Am J Hematol 2018 01 3;93(1):E22-E24. Epub 2017 Nov 3.

Department of clinical medicine and surgery, Federico II University, Naples NA, Italy.

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http://dx.doi.org/10.1002/ajh.24945DOI Listing
January 2018

Mixed T Cell Chimerism After Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using an Alemtuzumab-Containing Regimen Is Shaped by Persistence of Recipient CD8 T Cells.

Biol Blood Marrow Transplant 2017 Feb 2;23(2):293-299. Epub 2016 Nov 2.

Division of Cancer Studies, King's College London, London, United Kingdom. Electronic address:

Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90.7%. Acute and chronic GVHD each occurred in 6 patients (13.3%), and only 1 case was severe. Mixed T cell chimerism was frequent and persisted after cessation of immunosuppression. T cells were extensively depleted, representing only 11.3% of lymphocytes at day 30 and rising to 43.8% by 1 year, but still significantly below normal levels (67.2%; P = .018), and deficiency persisted after immunosuppressive therapy (IST) withdrawal. Depletion of CD4 T cells was particularly profound, causing inversion of the normal CD4:CD8 T cell ratio. T cell subset composition was also abnormal, with memory and effector T cells predominating for at least 6 months after FCC HSCT. Analysis of T cell subset chimerism showed that CD4 T cells were predominantly donor-derived at 1 year, whereas recipient-derived CD8 T cells shaped mixed chimerism with a notable contribution of recipient effector CD8 T cells. The prolonged mixed T cell chimerism after IST withdrawal and low incidence of GVHD indicates the establishment of mutual tolerance, but the low incidence of viral disease suggests maintenance of antiviral immunity. Our study shows that despite the abnormal T cell profile after allogeneic HSCT for SAA using the FCC regimen, this regimen is conducive to an excellent clinical outcome.
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http://dx.doi.org/10.1016/j.bbmt.2016.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270460PMC
February 2017

Twenty years of the Italian Fanconi Anemia Registry: where we stand and what remains to be learned.

Haematologica 2016 Mar 3;101(3):319-27. Epub 2015 Dec 3.

Genetics Unit, ASL Napoli 1, Naples, Italy

The natural history of Fanconi anemia remains hard to establish because of its rarity and its heterogeneous clinical presentation; since 1994, the Italian Fanconi Anemia Registry has collected clinical, epidemiological and genetic data of Italian Fanconi Anemia patients. This registry includes 180 patients with a confirmed diagnosis of Fanconi anemia who have either been enrolled prospectively, at diagnosis, or later on. After enrollment, follow-up data were periodically collected to assess the clinical course, possible complications and long-term survival; the median follow up was 15.6 years. The main goal of the study was to describe the natural history of Fanconi anemia, focusing on the following variables: family history, disease presentation, development of hematological manifestations, development of malignancies, occurrence of hematopoietic stem cell transplantation and survival. Typical morphological and/or hematological abnormalities and/or growth retardation were the most common manifestations at diagnosis; the majority of patients (77%) exhibited hematological abnormalities at the initial presentation, and almost all (96%) eventually developed hematological manifestations. More than half of the patients (57%) underwent a bone-marrow transplant. The occurrence of cancer was quite rare at diagnosis, whereas the cumulative incidence of malignancies at 10, 20 and 30 years was 5%, 8% and 22%, respectively, for hematological cancers and 1%, 15% and 32%, respectively, for solid tumors. Overall survival at 10, 20 and 30 years were 88%, 56% and 37%, respectively; the main causes of death were cancer, complications of the hematological presentation and complications of transplantation. These data clearly confirm the detrimental outcome of Fanconi anemia, with no major improvement in the past decades.
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http://dx.doi.org/10.3324/haematol.2015.133520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815723PMC
March 2016

Nonmyeloablative peripheral blood haploidentical stem cell transplantation for refractory severe aplastic anemia.

Biol Blood Marrow Transplant 2014 Nov 10;20(11):1711-6. Epub 2014 Jul 10.

Department of Hematological Medicine, King's College Hospital, London, United Kingdom; Department of Haematological Medicine, King's College London, London, United Kingdom. Electronic address:

New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.
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http://dx.doi.org/10.1016/j.bbmt.2014.06.028DOI Listing
November 2014

[New frontiers in aortic surgery].

G Ital Cardiol (Rome) 2012 Oct;13(10 Suppl 2):96S-100S

Dipartimento di Cardiochirurgia, IRCCS Policlinico San Donato, San Donato Milanese.

In cardiac surgery, aortic diseases represent an important chapter, and include treatments from the aortic valve to the descending aorta. The infra-diaphragmatic abdominal aorta, generally and historically, is the domain of vascular surgery. Despite the excellent and consolidated results obtained in the treatment of thoracic aortic disease, surgical mortality and morbidity are still relevant, also due to the presence of older patients with more extensive and complex aortic disease. In the last decades, the better knowledge of the aortic issues and the availability of new grafts have resulted in an important evolution of the management, both at the aortic valve and vessel level, with use of transcatheter grafts (transcatheter aortic valve implantation and thoracic endovascular aortic repair). The evidence of the right indications and the long-term results will determine the real usefulness and effectiveness of these "new" procedures and their role as safe and definitive aortic therapies.
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http://dx.doi.org/10.1714/1167.12929DOI Listing
October 2012

Efficacy and safety of rituximab treatment in patients with progressive transformation of germinal centers after Hodgkin lymphoma in complete remission post-induction chemotherapy and radiotherapy.

Leuk Lymphoma 2011 Nov 12;52(11):2082-9. Epub 2011 Jun 12.

Department of Biochemistry and Medical Biotechnology, Federico II University Medical School, Naples, Italy.

Because the lymphatic tissue of progressive transformation of germinal centers (PTGC) expresses CD20, rituximab treatment may prevent transformation to lymphoma of this rather atypical entity. We prospectively evaluated the efficacy of immunotherapy with rituximab (375 mg/m2 i.v. weekly for 4 consecutive weeks, followed by a single i.v. infusion of 375 mg/m2 every 3 months for 2 consecutive years) in 48 patients with biopsy-proven PTGC after Hodgkin lymphoma in complete remission post-induction therapy (4-6 courses of anthracycline-containing chemotherapy with radiotherapy). The event-free survival (EFS) of this series was compared with that of a historical cohort of 48 patients with PTGC developing after Hodgkin lymphoma in complete remission post-induction therapy, who underwent observation. At a median follow-up of 40 months, histology showed a malignancy in 27% of patients in the observation group (Hodgkin lymphoma, 13 patients) and in 2% of patients in the rituximab-protected group (non-Hodgkin lymphoma, one patient) (p ∼ 0.001). Rituximab was well tolerated in all treated patients. All relapses in the group not protected by immunotherapy involved the PTGC regions and non-contiguous nodal sites, which suggests that PTGC is a reservoir for malignant transformation and dissemination. The number needed to treat with rituximab to avoid one Hodgkin lymphoma relapse was four. Our study shows that prophylaxis with rituximab helps improve EFS in patients with PTGC and a history of Hodgkin lymphoma.
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http://dx.doi.org/10.3109/10428194.2011.582656DOI Listing
November 2011

Implications of acute kidney injury after heart transplantation: what a surgeon should know.

Eur J Cardiothorac Surg 2011 Dec 21;40(6):1355-61; discussion 1361. Epub 2011 Apr 21.

Department of Cardiac Surgery, University of Foggia, Foggia, Italy.

Objective: Data regarding risks and consequences of acute kidney injury (AKI) after cardiac transplantation are dismissingly few and unclear. This study defined the incidence, risk factors and prognostic implication of AKI in a single-center cohort operated on between January 1999 and December 2008.

Methods: Data from 307 consecutive recipients (mean age: 47.42 ± 13.58, 20.5% female, 18.9% diabetics, 19.5% with previous cardiac operations, 26.4% hospitalized, 78.4 ± 33.7 ml min(-1) preoperative glomerular filtration rate (eGFR)) were analyzed using multivariable logistic regression modeling. AKI was defined according to RIFLE (Risk, Injury, and Failure; and Loss, and End-stage kidney disease) criteria.

Results: RIFLE scores of I or F were detected in 14%, and continuous venovenous hemofiltration was needed in 6.1%. Risk factors for AKI were: previous cardiac operation (odds ratio (OR) 2.35; 95% confidence interval (CI), 1.11-4.9), blood transfusion (OR 1.08; 95% CI, 1.011-1.16), troponin I release >10 (OR 1.031; 95% CI, 1.001-1.064), length of ischemic time (OR 1.008; 95% CI, 1.011-1.16). Overall hospital mortality averaged 7.8% and overall 1-year mortality was 10.4%; both mortality rates increased with each RIFLE stratification (Normal 3.4%, RIFLE R = 7.1%; RIFLE I = 25.7%; and RIFLE F = 37.5% and Normal 5.6%, RIFLE R = 11.8%, RIFLE I = 25.7%, and RIFLE F = 37.5%, respectively). AKI proved independent predictors of both early and 1-year mortality. The burden of AKI significantly affected 1-year kidney function (Δ preoperative GFR-1-year GFR in AKI vs no AKI = -25.872 ± 22.54 vs -7.968 ± 34.18, p = 0.015).

Conclusions: AKI is a highly prevalent and prognostically important complication. Some of the risk factors for AKI identified may be modifiable.
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http://dx.doi.org/10.1016/j.ejcts.2011.02.068DOI Listing
December 2011

Thyroid V30 predicts radiation-induced hypothyroidism in patients treated with sequential chemo-radiotherapy for Hodgkin's lymphoma.

Int J Radiat Oncol Biol Phys 2012 Apr 20;82(5):1802-8. Epub 2011 Apr 20.

Institute of Biostructures and Bioimages, National Council of Research (CNR), Naples, Italy.

Purpose: Hypothyroidism (HT) is a frequent late side effect of Hodgkin's lymphoma (HL) therapy. The purpose of this study is to determine dose-volume constraints that correlate with functional impairment of the thyroid gland in HL patients treated with three-dimensional radiotherapy.

Methods And Materials: A total of 61 consecutive patients undergoing antiblastic chemotherapy and involved field radiation treatment (median dose, 32 Gy; range, 30-36 Gy) for HL were retrospectively considered. Their median age was 28 years (range, 14-70 years). Blood levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (ATG) were recorded basally and at different times after the end of therapy. For the thyroid gland, normal tissue complication probability (NTCP), dosimetric parameters, and the percentage of thyroid volume exceeding 10, 20, and 30 Gy (V10, V20, and V30) were calculated in all patients. To evaluate clinical and dosimetric factors possibly associated with HT, univariate and multivariate logistic regression analyses were performed.

Results: Eight of 61 (13.1%) patients had HT before treatment and were excluded from further evaluation. At a median follow-up of 32 months (range, 6-99 months), 41.5% (22/53) of patients developed HT after treatment. Univariate analyses showed that all dosimetric factors were associated with HT (p < 0.05). On multivariate analysis, the thyroid V30 value was the single independent predictor associated with HT (p = 0.001). This parameter divided the patients into low- vs. high-risk groups: if V30 was ≤ 62.5%, the risk of developing HT was 11.5%, and if V30 was >62.5%, the risk was 70.8% (p < 0.0001). A Cox regression curve stratified by two levels of V30 value was created (odds ratio, 12.6).

Conclusions: The thyroid V30 predicts the risk of developing HT after sequential chemo-radiotherapy and defines a useful constraint to consider for more accurate HL treatment planning.
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http://dx.doi.org/10.1016/j.ijrobp.2010.09.054DOI Listing
April 2012

Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury.

J Thorac Cardiovasc Surg 2009 Oct 1;138(4):965-70. Epub 2009 Jul 1.

Department of Cardiac Surgery, University of Foggia, Foggia, Italy.

Objectives: Recent authoritative studies suggested that low preoperative hemoglobin concentration may affect cardiac surgery outcomes. This study aimed, primarily, to investigate whether preoperative anemia is an independent determinant of adverse events after coronary artery bypass grafting and, secondarily, to evaluate the potential dose responsiveness between anemia severity and primary end points.

Methods: This single-center prospective study investigated 1214 consecutive patients undergoing coronary artery bypass grafting between January 2004 and June 2007, collecting 100 variables per patient. In 1047 patients (median age 64 years, 18.8% female, 38.9% diabetic, 31.9% urgent/emergency, 15.3% with low preoperative left ventricular ejection fraction) who underwent on-pump procedures and received no preoperative transfusion, the prevalence of preoperative anemia (according to World Health Organization definition) and its unadjusted and adjusted relationships with in-hospital death, cardiac morbidity, and acute kidney injury (AKI-RIFLE [Risk, Injury, Failure, Loss, End-stage kidney disease] criteria) were obtained.

Results: The prevalence of preoperative anemia was 28%. In-hospital death averaged 3.9%, cardiac morbidity 7.3%, and acute kidney injury 4%. Unadjusted odds ratios (Ors) for in-hospital death, cardiac morbidity, and acute kidney injury were 3.8 (95% confidence interval [CI] 2.0-7.3), 1.7 (95% CI 1.1-2.8), and 4.0 (95% CI 2.1-7.6), respectively. Adjusting for anemia in confounders proved an independent predictor of acute kidney injury (OR 2.06; 95% CI 1.14-3.70), whereas the cardiac morbidity and in-hospital mortality were independently predicted by kidney function. No dose-response relationship emerged between anemia severity and acute kidney injury.

Conclusions: Preoperative anemia is independently associated with acute kidney injury after coronary artery bypass grafting. Further studies are warranted to determine whether preoperative low hemoglobin concentration is a marker of severity of illness or a modifiable risk factor.
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http://dx.doi.org/10.1016/j.jtcvs.2009.05.013DOI Listing
October 2009

Contrast-enhanced harmonic compound US of the spleen to increase staging accuracy in patients with Hodgkin lymphoma: a prospective study.

Radiology 2009 May;251(2):574-82

Departments of Biochemistry and Medical Biotechnology, Histopathology, and Oncology, Federico II University Medical School, and Fondazione SDN, Naples, Italy.

Purpose: To prospectively compare contrast material-enhanced harmonic compound ultrasonography (US), computed tomography (CT), and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting nodular infiltration in the spleen of patients with newly diagnosed Hodgkin lymphoma.

Materials And Methods: After institutional review board approval and informed consent, 100 consecutive patients with Hodgkin lymphoma during pretreatment staging were prospectively investigated for possible spleen involvement by comparing harmonic compound US (integrated with intravenous infusion of microbubbles in 33 patients) with CT and FDG PET. Findings indicative of malignant nodules with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, response to treatment was regarded as evidence of lymphoma.

Results: Malignant nodules were detected with CT in 13 patients, with FDG PET in 13 patients, and with contrast-enhanced harmonic compound US in 30 patients. Coincidental findings of malignancy with all three imaging techniques occurred in 13 patients; 17 patients had only US-detectable malignant nodules, which showed disappearance or relevant decrease after chemotherapy. Overall, the spleen had nodular infiltration in 30 patients (13 for imaging finding concordance; 17 for typical contrast-enhanced harmonic compound US findings and chemotherapy-related nodule size modifications). Thus, both CT and FDG PET provided false-negative results in 17 of 30 patients compared with contrast-enhanced harmonic compound US, the results of which translated into disease upstaging in 13 patients.

Conclusion: Harmonic compound US with contrast enhancement for the characterization of possible nodules provides a higher sensitivity than does CT or FDG PET in the detection of splenic involvement by Hodgkin lymphoma.
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http://dx.doi.org/10.1148/radiol.2512081293DOI Listing
May 2009

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.

Ann Hematol 2009 Feb 16;88(2):151-8. Epub 2008 Aug 16.

Hematology, Università Federico II, Naples, Italy.

A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling, and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible.
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http://dx.doi.org/10.1007/s00277-008-0571-zDOI Listing
February 2009