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  • 1
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4579-4579
    Abstract: Introduction Allogeneic stem cell transplantation (HCT) survivors are at a relevant risk of developing long-term complications such as chronic GvHD (cGvHD), which importantly affects their quality of life and increases their morbidity and mortality. Being able to early identify high risk patients would enable us to tailor preventive strategies. Current approach on prophylaxis of GvHD is lacking of predictive biomarkers that could guide patient-tailoring of drugs choice, tapering and treatment schedules. Immune system is the cause of cGvHD but is also a target of it, and cGvHD patients are characterized by lymphoid hypocellularity. Moreover, immune reconstitution (IR) is a good candidate biomarker being it an easily-available and reproducible parameter. We investigated IR variables as predictive biomarker of cGvHD. Methods A standardized follow-up of HCT-survivors is applied at our center. We analyzed 307 adult patients consecutively undergoing first allogeneic HCT transplant between July 2012 and December 2016 at our Institution. A written consent was given for the use of medical records for research in accordance with the Declaration of Helsinki. Median follow-up for surviving patients was 2.8 years (range 1.1-5.5). We prospectively collected IR data of our entire cohort at specific time-points (+30, +60, +90, +180, +365 days) and followed patients up recording events. IR variables were CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD56+ cell counts, measured by flow-citometry, and immunoglobulins IgG, IgA and IgM levels, measured by immunoturbidimetric assays. Time as a continuous parameter could not be studied since the number of events would have been too low for the analysis. For this reason, a series of landmark analyses were performed at 3, 6 and 12 months post-HCT in order to identify predictive factors of cGvHD, transplant-related mortality (TRM), progression-free survival (PFS) and overall survival (OS) for patients alive and in good conditions at the beginning of each time interval. Factors predicting cGvHD incidence and survival endpoints were studied using multivariate analysis by Cox regression model. Variables included in the model were patient and donor age and Sorror-Comorbidity Index (according to median values), disease-related index, type of donor, stem cell source, IR values at the timepoint according to landmark cut-off for cell counts and median values for immunoglobulin levels. A backward stepwise procedure was used for variable selection with a p-value 〈 0.05. All statistical analyses were performed with R (R Development Core Team, Vienna, Austria) software package. Results Chronic-GvHD of any grade and severity was diagnosed in 111 patients. Immune recovery in our cohort was in line with the current knowledge: CD3+CD8+ and NK (CD56+) cells normalized first, followed by CD3+ and CD3+CD4+ cell. B cells (CD19+) took at least 1 year to normalize in terms of absolute counts. IgM levels were the first to rise among immunoglobulins, followed by IgG and then IgA which can also be subnormal for a long time after transplant. Results of multivariate analysis are shown in Table 1. Single lymphocyte subset counts did not prove to be associated to cGvHD onset significantly; conversely, immunoglobulins were strongly predictive of cGvHD in our multivariate model. Median time to GvHD onset was 198 days, thus the most important analysis was the one performed at +90 days as the majority of patients had still not developed cGvHD. IgG, IgA and IgM at +90 days from HCT below the median value were found before the onset of GvHD and could predict its onset. This data were confirmed on the analysis at later time-points in which low IgG levels predicted cGvHD diagnosis. Conclusions Day-90 low immunoglobulin levels predict cGvHD, confirming that subclinical immune dysregulation mechanisms could be already present before overt clinical onset of cGvHD symptoms. Early prediction of subsequent cGvHD will be operationally translated into patient-tailored preventive measures. Disclosures Bonini: Intellia Therapeutics: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 2
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4600-4600
    Abstract: Introduction Allogeneic stem cell transplantation (allo-HCT) survivors are at a defined relevant risk of developing long-term complications: the prevalence of chronic health conditions approaches 75% among HCT survivors. The endocrine system is one of the most frequent targets of complications, providing justification for a long-term and continuous follow-up (LTFU) to assure a timely and appropriate treatment. The aim of our study is to evaluate the incidence of endocrinopathies in survivors in respect of sex, age, donor type, conditioning regimen and GvHD occurrence. Methods A standardized LTFU is applied at our center. We here analyze data consecutively collected in an Institutional database, starting from 2006, including 402 adult patients (pts) who underwent an allo-HCT between 1992 and 2016 at our Institution. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. We considered for the analysis pts with an overall survival 〉 /=1y. We reviewed pts chapters with a focus on occurrence, management and treatment of diabetes, thyroid disfunctions, dyslipidemia and osteopenia / osteoporosis: diagnosis and follow-up were performed according to guidelines for long-term HCT survivors. Results With a median follow-up of 7y (r 2-25y) 328 pts were evaluable; donor was a match unrelated donor in 107 cases, HLA identical sibling in 88, haploidentical relative in 129 and cord blood in 4. The 5y-incidence of diabetes type 2 was 3%, with a median time after allo-HCT of 1138 days (r 5-4181 days); 13/22 developed diabetes after diagnosis of GvHD (median time 884 days, r 30-3753 days). All pts received indication for diet modification, 11 pts were treated with insulin and 8 pts with metformin. Thyroid disfunction was documented in 38 pts (5y-incidence 8,5%): 2 pts were diagnosed with hyperthyroidism and treated with methimazole or radioiodine treatment. Hypothyroidism was documented in 36 pts (median time after allo-HSCT 799 days, r 65-5021 days). Thirteen pts developed hypothyroidism following the diagnosis of GvHD (median time 1236 days, r 166-3540 days). Only 2 pts did not receive a specific treatment, while all the others received substitutive therapy with levothyroxine. Furthermore 1 pt was diagnosed with a papillary thyroid cancer. The 5y-incidende of dyslipidemia was 30% with a median time after allo-HSCT of 1433 days (r 366-7629), 47 pts developed dyslipidemia after the diagnosis of GVHD (median time 1425 days, r 134-7403 days). Diet-therapy was recommended to all the pts, 29 pts received a statin-based pharmacological treatment, 20 pts a polyenoic-fatty-acids based treatment, while a nutraceutical compound was given in 13 pts. Osteopenia was documented in 120 pts (median time after allo-HSCT 994 days, range 31-6605 days) with a 5y-incidence of 36%. Seventy-nine pts presented osteopenia after diagnosis of GvHD (median time after GvHD diagnosis 707 days, r 13-6379 days). Eight pts did not receive a specific treatment. Two pts received treatment with biphosphonates plus oral vitamin D and calcium supplementation, the 110 remaining pts received oral vitamin D +/- calcium supplementation only. Sixty-four pts developed osteoporosis (median time after allo-HSCT 1000 days, r 60-8836 days), the 5y-incidence was 26%. Forty-four pts developed osteoporosis following the diagnosis of GvHD (median time 724 days, r 28-8280 days). Only 4 pts did not receive any specific therapy; 31 pts received therapy with bisphosphonates, 2 pts denosumab and 27 pts oral vitamin D and calcium supplementation. In univariate analysis no relationship between host sex, age at transplant, TBI exposure, donor or history of GvHD and development of diabetes, thyroid disfunction and dyslipidemia was outlined. Otherwise, osteopenia development was strongly associated with GvHD occurrence and osteoporosis was strongly associated with age, sex and GvHD occurrence (table 1). Conclusions Allo-HCT survivors are at relevant risk of endocrinopathies after transplantation, providing justification for specific monitoring to individualize treatment and follow-up. Of note, classical transplant-related variables are not enough to justify the occurrence of endocrinological disfunction: a further deeper evaluation of a misdiagnosed donor-mediated autoimmune predisposition will be essential. Disclosures Bonini: Intellia Therapeutics: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 3
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5810-5810
    Abstract: Introduction Tyrosine kinase inhibitor (TKi) has become the standard of care in patients (pts) with chronic myeloid leukemia (CML) and an unavoidable tool in the combined therapy for pts with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Nevertheless, because of resistance to TKI and side-effects, allogeneic stem cell transplantation (HSCT) remains the standard therapy of ALL Ph+ and of CML pts failing 1st line therapy with TKi, with failure or insufficient response or intolerance or mutations resistant to 2nd generation TKI, or in the advanced phase at diagnosis (accelerated phase and blast crisis). Unfortunately, despite greater remission with the use of TKi pre-transplant, HSCT transplant outcome have not improved largely due to high incidence of relapse after transplant. In the past decade several multi-institutional studies confirmed the feasibility and safety of post-HSCT imatinib administration as prophylactic or therapeutic strategy. Second and 3rd generation TKi administration after HSCT - targeting mutational status and according to pre-HSCT activity - is today under investigation. Methods Here we are reporting our experience in post-HSCT treatment with the 3rd generation TKi ponatinib in 5 pts (4 CML, 1 ALL Ph+) treated between 2011 and 2016 at our Institution. Pts data and information were collected from Institutional database and chapters revision. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. Results Pts and diseases features are reported in table 1. Stem cell source was peripheral blood in all cases, 3 pts were transplanted from a family mismatched donor (haplo), 1 from a family matched donor, 1 from a matched unrelated donor (MUD). The 3 haplo-transplanted pts previously underwent a MUD HSCT. All pts received a treosulfan based conditioning regimen and GvHD prophylaxis consisted on co-administration of MMF and rapamycin. Pre-transplant treatment for the ALL Ph+ consisted of chemotherapy combined with dasatinib, followed by a first MUD HSCT and dasatinib in maintenance. The patient relapsed 1 year after HSCT with documentation of mutation V299L. Ponatinib was introduced as salvage treatment to bridge second haplo HSCT. Pre-transplant treatment for the CML patients consisted of TKi therapy with combination of chemotherapy in case of uncontrolled progression of disease. Two pts received a first MUD HSCT but relapsed respectively 5 months and 4 years later. Four pts received ponatinib 45 mg daily before the last HSCT: one patient achieved sustained major molecular response, 3 pts obtained transient response. All pts were presenting 2nd generation TKi resistant mutation (ref table 1). Ponatinib was started at a median time of 157 days after HSCT (range, 117-583): in 3 cases as salvage treatment in overt relapse, while in one case as prophylaxis and one case as preemptive therapy. Acute GvHD was diagnosed in 4 pts before ponatinib administration, 2 of them also experienced chronic GvHD. No new cases of GvHD were observed after initiation of ponatinib. Immunosuppressive treatment and azoles treatment were discontinued before ponatinib in all but one patient who was under combined treatment for chronic GvHD: therapeutic drug monitoring was closely performed without evidence drug-drug interaction. Pts were regularly evaluated for toxicities. No serious adverse events were reported in our experience: we administered ponatinib at a median maximum dosage of 30 mg daily (range, 15-45 mg), for a median of 24 weeks (range, 4 - 116 weeks). Two pts required anti hypertension drugs. One patient was closely monitored for multifactorial liver cholestasis never requiring ponatinib discontinuation. At last evaluation one patient maintained the status of molecularly undetectable leukemia (follow-up post HSCT 30 months) and two pts obtained molecular response (follow-up post HSCT 25 months and 5 months). Two patients who received therapeutic ponatinib in overt relapse didn't respond and died for progressive disease. Conclusions Ponatinib is safe and well tolerated as bridge to HSCT and to maintain the disease control after transplant. Prophylaxis targeted therapy and pre-emptive therapy with ponatinib may lead the reduction of disease relapse for high-risk Ph+ leukemia. Disclosures Bonini: Molmed SpA: Consultancy; TxCell: Membership on an entity's Board of Directors or advisory committees. Ciceri:MolMed SpA: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 4
    In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 108, No. 6 ( 2022-10-06), p. 1530-1543
    Abstract: After allogeneic hematopoietic stem cell transplantation (HSCT), the emergence of circulating cytomegalovirus (CMV)- specific T cells correlates with protection from CMV reactivation, an important risk factor for non-relapse mortality. However, functional assays measuring CMV-specific cells are time-consuming and often inaccurate at early time-points. We report the results of a prospective single-center, non-interventional study that identified the enumeration of Dextramerpositive CMV-specific lymphocytes as a reliable and early predictor of viral reactivation. We longitudinally monitored 75 consecutive patients for 1 year after allogeneic HSCT (n=630 samples). The presence of ≥0.5 CMV-specific CD8+ cells/mL at day +45 was an independent protective factor from subsequent clinically relevant reactivation in univariate (P 〈 0.01) and multivariate (P 〈 0.05) analyses. Dextramer quantification correlated with functional assays measuring interferon-γ production, and allowed earlier identification of high-risk patients. In mismatched transplants, the comparative analysis of lymphocytes restricted by shared, donor- and host-specific HLA revealed the dominant role of thymic-independent CMV-specific reconstitution. Shared and donor-restricted CMV-specific T cells reconstituted with similar kinetics in recipients of CMV-seropositive donors, while donor-restricted T-cell reconstitution from CMV-seronegative grafts was impaired, indicating that in primary immunological responses the emergence of viral-specific T cells is largely sustained by antigen encounter on host infected cells rather than by cross-priming/presentation by non-infected donor-derived antigen-presenting cells. Multiparametric flow cytometry and high-dimensional analysis showed that shared-restricted CMV-specific lymphocytes display a more differentiated phenotype and increased persistence than donor-restricted counterparts. In this study, monitoring CMV-specific cells by Dextramer assay after allogeneic HSCT shed light on mechanisms of immune reconstitution and enabled risk stratification of patients, which could improve the clinical management of post-transplant CMV reactivations.
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2022
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  • 5
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4400-4400
    Abstract: Background Optimization of pre-transplant risk assessment is a crucial issue to improve the allo-HSCT decision making process. Actually 3 major algorithms are in use in clinical practice: the EBMT risk score, the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and - more recently introduced - the refined Disease Risk Index (DRI). DRI was defined to calibrate HSCT outcome across studies and centers. It was developed as a tool to assign patients into risk groups based on disease type and status at the time of transplantation. The aim of the DRI is to provide a robust tool that can be used for prognostication, for the analysis and interpretation of retrospective data, whether conducted in single-center, multicenter, or registry settings, or within the context of the federally mandated center outcome reporting. The DRI can also be used for the stratification of patients entering prospective HCT clinical trials. DRI is not a fixed tool but instead it was conceived to be refined by the transplant community as new information becomes available. Here we are presenting the results of a retrospective study designed to evaluate the 3 aforementioned score in stratification and prognostication of transplant outcome after a haploidentical HSCT (haplo-HSCT). Patients and Methods We included 220 adult patients (pts - 138 male, 82 female) who underwent a haplo-HSCT for hematologic malignancies, between 2006 and 2014 and were reported to our Institutional database. Risk assessment score and outcome analysis included all consecutive pts receiving an haplo-HSCT as 1st allogeneic transplantation. Pts receiving haplo-HSCT as 2nd or 3rd HSCT were excluded from the present analysis. Median age was 49 years (range, 15-77). The cohort included a broad representation of diseases (138/220 acute leukemia, 30 Hodgkin lymphoma); 62 pts were in complete remission at transplant, 158 were presenting active disease. Conditioning regimens mostly rely upon the combination of treosulfan plus fludarabine (201/220) and total body irradiation (range 200 - 400 cGy) was utilized in 52 patients. GVHD prophylaxis consisted mostly of an mTor inhibitor (rapamycin) combined with mycophenolate mofetil. The majority of patients received peripheral blood stem cells from a family haploidentical donor as stem cell source, while only 4 patients received bone marrow transplant. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. Results The median follow-up for survivors was 37 months (r 6-107). The overall survival (OS) at 2-y was 35% and the transplant related mortality at 100-days 23%. The 2y OS according to EBMT / HCT-CI / DRI risk score are reported in table 1.a and figure 1. The evaluation of the HCT-CI impact after DRI stratification was able to show a significant difference in outcome showing better survival for pts with low DRI score and low HCT-CI score as expected (table 1.b). Discussion Refined DRI score and HCT-CI score predict survival after haplo-HSCT. The integrated application of refined DRI and HCT-CI may improve the definition of transplant eligibility for pts candidate to allogeneic HSCT form alternative donors including family haploidentical source. Table 1a. EBMT score 0-3 % pts 4-5 %pts 〉 5 %pts p 51% 17 34% 51 27% 32 0.07 HCT-CI score 0-2 3-4 〉 /= 5 48% 59 36% 31 0% 10 0.0001 DRI score Low-Intermediate High Very-High 61% 32 27% 51 5% 17 0.0001 Table 1b. HCT-CI 0-4 HCT-CI 〉 /=5 p DRILow-Intermediate 64% 0% 0.0001 DRIHigh-Very High 29% 0% Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 6
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3492-3492
    Abstract: Introduction Pre-transplant risk assessment is a crucial issue to improve the HCT decision-making process. Several transplant-related models have been designed to optimize decision-making about suitable candidates for allogeneic HCT. The refined Disease Risk Index (DRI) was developed to stratify disease risk acrosshistologiesand HCT regimens. However, few recipients of haploidentical HCT were originally included in the DRI study cohorts. In 2015 a first large cohort of non-myeloablativehaploidentical HCT with post-transplant cyclophosphamide (PTCy) confirmed the validity of DRI also in this setting. Beside this, in the past few years the novel composite end point of GVHD-free, relapse-free survival (GRFS) after HCT spreads out. GRFS acknowledge that both survival and rates of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death are clinically meaningful. GRFS therefore represents ideal recovery from HCT and a measure of cure without ongoing morbidity. Methods We analyzed risk-stratified GRFS according to the refined DRI in haploidentical HCT at our Center, where it was exploited - since 2006 - asirolimus-based,calcineurininhibitor-free prophylaxis of GvHD to allow the safe infusion of unmanipulated haploidentical HCT. We analyze data collected between 2006 and 2014 including 207 adult pts. Data were prospectively collected in Institutional database. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. All consecutive pts receiving a haplo HCT as 1st allogeneic transplantation were included - pts receiving haplo HCT as 2nd or 3rd HCT were excluded from the present analysis. Results Baseline characteristics of the 207 pts are outlined in table 1. With 4-year median follow-up, 4-year probabilities of transplant related mortality (TRM),relapse, progression-free survival (PFS), and overall survival (OS) were 25,8%, 42,5%, 31,7%, and 34,4%, respectively. Day-100 cumulative incidence of grade II-IV and III-IV acute graft-versus-host-disease (GvHD) were 30,1% and 15,5% respectively. The 4-year cumulative incidence of chronic GvHD was 33,5% (moderate-severe chronic GvHD 26,2%). Considering the composite end point of GRFS, for the entire population the 4-year GRFS was 17,8%. By refined DRI group, low-intermediate (n 69), high (n 105), and very high (n 33) risk groups had 4-year GRFS estimates of 31,1%, 13,7%, and 3,0% (p 〈 .0001), with corresponding 4-year OS estimates of 56,7%, 28,9%, and 6,1% (p 〈 .0001). On a multivariable Cox model we considered as covariates age, host/donor sex mismatch, host/donor CMV status, stem cell source, conditioning intensity, GvHD prophylaxis ATG-based versusPTCy-based, DRI stratification, HCT Comorbidity Index Score (HCT-CI). On multivariable analyses, the DRI was statistically significantly associated with GRFS, OS, PFS, relapse, TRM and grade II to IV acute GvHD (ref table 2). HCT-CI was statistically significantly associated with GRFS, OS, PFS and TRM. Conditioning intensity was associated with PFS and relapse, while GvHD prophylaxis (PTCyvs ATG) was only associated with OS. Interestingly no risk factors were clearly emerging for chronic GvHD. Conclusions The combination of a refined DRI and GRFS provide a valid tool to improve the HCT decision-making process and will help optimize patient outcomes. Disclosures Ciceri: MolMed SpA: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 7
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 10 ( 2022-05-24), p. 3053-3057
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 8
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3442-3442
    Abstract: Introduction Voriconazoleis a second-generationtriazolebroad-spectrum antifungal agent indicated in adults and children aged 2 years and above as treatment of invasive aspergillosis, treatment ofcandidaemiain non-neutropenic patients (pts), treatment of fluconazole-resistant serious invasive Candida infections, treatment of serious fungal infections caused byScedosporiumspp. and Fusarium spp. Voriconazoleis associated with a broad spectrum of dermatologically adverse reactions: it seems to be responsible for a multistep process beginning with acute and chronicphototoxicity, followed by actinic keratosis (AK), and finally skin squamous cell carcinoma (SCC), especially if therapy is maintained. Strictphotoprotectionis mandatory; drug replacement by anothertriazolemust be discussed in case of acutephototoxicity.Voriconazolemust be stopped in pts with chronicphototoxicity, and a long-term dermatologic follow-up of skin lesions is required even after withdrawal. It is now established thatvoriconazoleis an independent risk factor for the development of cutaneous malignancy in lung transplant recipients. Recently, a retrospective study from the Mayo Clinic (WojenskiDJ et al, Transplant Infectious Disease 2015, 17, 250-58) confirmed the association betweenvoriconazoleand SCC also after allo-HSCT (allogeneic hematopoietic stem cell transplantation) and identified cumulative days ofvoriconazoleas a risk factor for SCC. Methods The current study seeks to analyze the correlation betweenvoriconazoleexposure and non-melanoma skin cancer (NMSC) in our Center, where it is available an intensive dedicated follow-up after allo-HSCT to prevent and early detect second solid tumors. Results We analyze data prospectively collected at our Long-Term Follow-Up clinic between 2011 and 2016 including 302 adult pts with a minimum follow-up of 24 months. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. Baseline characteristics of the 302 pts are outlined in table 1. In total, 25 pts developed NMSC - median time from allo-HSCT 42 months (range, 9 months - 20 years) - median follow-up after NMSC diagnosis 2 years (range, 2 months - 12 years). The estimated cumulative incidence of NMSC at 3 years was 3.2% and at 5 years 6.2%. At the dermatological annual evaluation 3 pts were presenting AK, only one progress to basal cell carcinoma (BCC), the 2 pts with AK are under dermatological follow-up. All pts were treated withvoriconazolefor more than 180 days. In total 19 pts were diagnosed with BCC and 6 pts with SCC. Five pts with SCC and 17 with BCC were treated withvoriconazole, overall 16/22 (4 SCC) for more than 180 days. All pts were treated according to standard practice for NMSC, unfortunately 1 pts deceased due to SCC progression. Only 2 pts were diagnosed and treated for NMSC before transplantation. Six pts had antecedent acute GvHD and 8 pts had antecedent moderate to severe chronic GvHD. History ofvoriconazoleexposure, cumulative days ofvoriconazoleuse, gender, age at transplant, TBI based conditioning regimen, acute/chronic GvHD and skin cancer pre-transplant were considered for analysis. Age at transplant above 48 years (p 〈 0.0001),voriconazoleexposure (p 0.0088) and cumulative days ofvoriconazoleexposure greater than 180 days (p 0.0038) were associated with higher risk of NMSC. Conclusions Our experience confirms the correlation betweenvoriconazoleand occurrence of NMSC after allo-HSCT. Incidence of NMSC is higher than previously reported in registry reports, and the occurrence of NMSC in pts exposed tovoriconazoleseems to be precocious. This observation confirms the relevance of counseling and prevention of NMSC in patients benefiting fromvoriconazoleas a crucialmold-active antifungal prophylaxis and treatment. Disclosures Bonini: Molmed SpA: Consultancy; TxCell: Membership on an entity's Board of Directors or advisory committees. Ciceri:MolMed SpA: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 9
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4362-4362
    Abstract: Introduction Allogeneic hematopoietic cell transplantation (HCT) is an effective therapeutic option for high-risk hematological malignancies; 80% of those who survive the first 2 years are expected to become long-term survivors. The prevalence of chronic health conditions approaches 75% among HCT survivors and that for severe or life-threatening conditions exceeds 20%. Patients and Methods A standardized follow-up of HCT survivors is applied at our Center, according to Jacie Standards. Here we report the analysis of data collected between July 2014 and July 2015 in 260 adult patients (pts) who underwent an HCT between 1992 and 2014. Data on 7 items - selected to monitor relevant comorbidities - were prospectively collected in our Institutional database. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. Results Pts characteristics are reported in table 1, median time of follow-up 4.4y (r1-22), cumulative follow-up 1404y; 13 pts deceased during the time of observation (6 due to disease relapse, 2 to late major infection, 2 to second cancer, 1 to GvHD, 1 to myocardial infarction, 1 unknown). - chronic Graft-versus-Host-Disease (c-GvHD): at a median follow-up of 43 months (r 16 months - 21 years) 84 (32%) pts are presenting c-GvHD features. According to NIH 2014 consensus criteria 23 cases were classified as mild, 32 moderate, 29 severe. Median number of involved organs 2 (r1-5), 39 pts were experiencing skin lesions, 55 eyes, 28 mouth, 19 joint and fascia, 18 lungs. Topical therapy was the treatment of choice for mild cases, while moderate and severe were treated with systemic therapy. The partnership with the lung specialist and the ophthalmologist was crucial for the management of lung and eyes GvHD. - Late infectious manifestation: 38 (15%) pts present late infection, 2 pts deceased due to major events. Of note pneumonia was reported in 12 pts, Varicella Zoster virus reactivation in 7, CMV late reactivation in 4 pts. - Second cancer screening was performed according to international guidelines. The incidence of new cases is 10% (26 pts) and 11 pts are actually under work-up for suspicious lesions. Non-melanoma skin cancer was the most frequent diagnosis (13 cases); 3 pts were diagnosed with cervix cancer, 2 with lung cancer. The prevalence of second cancer in our population is 18% (47 cases). All pts were treated according to standard for general population, 45/47 are alive. - Cardiovascular diseases were frequently observed in our setting: hypertension was documented in 36 pts, arterial diseases in 10 pts, cardiomyopathy in 28 pts. Overall 27% of pts were diagnosed with cardiovascular comorbidities. - Metabolic syndrome (MS) is reported as a very common complication in long-term survivors: 65 (25%) pts were presenting features of MS (3/5 among hypertension, dyslipidemia, raised fasting glucose, and central obesity). A concomitant thyroid dysfunction - requiring hormonal replacement - was present in 27/65 pts. - Secondary hemosiderosis was documented (with MRI and blood parameters) and treated in 39 pts (15%) - 8 pts received deferasirox while phlebotomy was used in 31. - Osteoporosis and bone loss were evaluated measuring bone mineral density using dual-energy X-ray absorptiometry; osteopenia was detected in 81 pts and osteoporosis in 42 (47%). Pts were evaluated in conjunction with the endocrinologist and treated according to the fracture risk score. According to donor source no difference were observed (Chi-square test - p ns) except for higher incidence of moderate/severe GvHD incidence in HLA identical sibling (p 0.0097) as compared to alternative donors. Discussion HCT survivors are at a defined relevant risk of developing long-term complications that have a direct impact on the morbidity and mortality.A multidisciplinary active screening within routine HCT long-term follow-up care is mandatory to enhance early diagnosis/treatment and overall outcome. The next challenge will be to enhance the primary prevention to reduce the incidence of preventable comorbidities. Table 1. patients characteristics N (range) Pts 260 Age At transplant 48y (10 - 76) At follow-up 54y (20 - 82) Male / Female 169 / 91 Diagnosis AML / ALL 106 / 33 MDS 27 HD / NHL 23 / 29 MM 14 CML 8 CLL 5 SAA / EPN 4 / 1 Others 10 Status at transplant CR / PD 169 / 91 Donor Haploidentical 100 HLA identical Sibling 76 Match Unrelated Donor 82 Cord Blood 2 Disclosures Bonini: MolMed S.p.A: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 22, No. 3 ( 2016-03), p. S189-S190
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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