Publications by authors named "Ilaria Scortechini"

20 Publications

  • Page 1 of 1

Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases.

Eur J Haematol 2020 Dec 30. Epub 2020 Dec 30.

Biothecnology Research Unit, AO of Cosenza, Cosenza, Italy.

Objectives: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only.

Methods: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study.

Results: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P = .04) independent of potential confounders.

Conclusions: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.
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http://dx.doi.org/10.1111/ejh.13573DOI Listing
December 2020

Severe COVID-19 in a patient with chronic graft-versus-host disease after hematopoietic stem cell transplant successfully treated with ruxolitinib.

Transpl Infect Dis 2021 Feb 14;23(1):e13401. Epub 2020 Jul 14.

Hematology and Stem Cell Transplant, Ancona University Hospital, Ancona, Italy.

Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplant, which is known to be mediated by cytotoxic T-cell effectors and dysregulated inflammatory cytokines. Similarly, the lung injury observed in severe COVID-19 cases appears to be related to a massive production of pro-inflammatory cytokines. The selective JAK1/2 inhibitor ruxolitinib has shown promising results in the context of GVHD, and different trials are currently underway in patients with severe COVID-19; nevertheless, no clinical observation of safety or efficacy of treatment with ruxolitinib in this context has been published yet. We describe a first case of severe COVID-19 developed after hematopoietic stem cell transplantation in a patient with a concomitant chronic GVHD (cGVHD), in which a treatment with ruxolitinib was administered with good tolerance and positive outcome.
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http://dx.doi.org/10.1111/tid.13401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361240PMC
February 2021

Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

Oncotarget 2018 May 4;9(34):23443-23450. Epub 2018 May 4.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.
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http://dx.doi.org/10.18632/oncotarget.25215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955107PMC
May 2018

Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties.

Bone Marrow Transplant 2019 01 4;54(1):44-52. Epub 2018 May 4.

EBMT Chronic Malignancies Working Party, Leiden, Netherlands.

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.
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http://dx.doi.org/10.1038/s41409-018-0207-4DOI Listing
January 2019

Immunomodulatory Effects of Tyrosine Kinase Inhibitor In Vitro and In Vivo Study.

Biol Blood Marrow Transplant 2018 02 8;24(2):267-275. Epub 2017 Nov 8.

Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy; Clinica di Ematologia, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy. Electronic address:

Pathogenesis of chronic graft-versus-host disease (cGVHD) is incompletely defined, involving donor-derived CD4 and CD8-positive T lymphocytes as well as B cells. Standard treatment is lacking for steroid-dependent/refractory cases; therefore, the potential usefulness of tyrosine kinase inhibitors (TKIs) has been suggested, based on their potent antifibrotic effect. However, TKIs seem to have pleiotropic activity. We sought to evaluate the in vitro and in vivo impact of different TKIs on lymphocyte phenotype and function. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured in the presence of increasing concentrations of nilotinib, imatinib, dasatinib, and ponatinib; in parallel, 44 PBMC samples from 15 patients with steroid-dependent/refractory cGVHD treated with nilotinib in the setting of a phase I/II trial were analyzed at baseline, after 90, and after 180 days of therapy. Flow cytometry was performed after labeling lymphocytes with a panel of monoclonal antibodies (CD3, CD4, CD16, CD56, CD25, CD19, CD45RA, FoxP3, CD127, and 7-amino actinomycin D). Cytokine production was assessed in supernatants of purified CD3 T cells and in plasma samples from nilotinib-treated patients. Main T lymphocyte subpopulations were not significantly affected by therapeutic concentrations of TKIs in vitro, whereas proinflammatory cytokine (in particular, IL-2, IFN-γ, tumor necrosis factor-α, and IL-10) and IL-17 production showed a sharp decline. Frequency of T regulatory, B, and natural killer (NK) cells decreased progressively in presence of therapeutic concentrations of all TKIs tested in vitro, except for nilotinib, which showed little effect on these subsets. Of note, naive T regulatory cell (Treg) subset accumulated after exposure to TKIs. Results obtained in vivo on nilotinib-treated patients were largely comparable, both on lymphocyte subset kinetics and on cytokine production by CD3-positive cells. This study underlines the anti-inflammatory and immunomodulatory effects of TKIs and supports their potential usefulness as treatment for patients with steroid-dependent/refractory cGVHD. In addition, both in vitro and in vivo data point out that compared with other TKIs, nilotinib could better preserve the integrity of some important regulatory subsets, such as Treg and NK cells.
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http://dx.doi.org/10.1016/j.bbmt.2017.10.039DOI Listing
February 2018

Combination of bendamustine and rituximab as front-line therapy for patients with chronic lymphocytic leukaemia: multicenter, retrospective clinical practice experience with 279 cases outside of controlled clinical trials.

Eur J Cancer 2016 06 27;60:154-65. Epub 2016 Apr 27.

UOC Ematologia, Ospedale Annunziata, Cosenza, Italy. Electronic address:

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region (IGHV) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials.
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http://dx.doi.org/10.1016/j.ejca.2016.03.069DOI Listing
June 2016

Reversal of poor graft function with iron-chelating therapy after allogeneic transplantation for severe aplastic anemia.

Leuk Lymphoma 2016 23;57(4):965-8. Epub 2015 Dec 23.

a Clinica di Ematologia, Università Politecnica Delle Marche , Ancona , Italy ;

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http://dx.doi.org/10.3109/10428194.2015.1085530DOI Listing
December 2016

Mobilization-driven postconsolidation therapy in elderly patients with acute myeloid leukemia: feasibility and efficacy of autologous stem cell transplantation versus low-dose gemtuzumab ozogamicin.

Biol Blood Marrow Transplant 2014 Sep 28;20(9):1399-406. Epub 2014 May 28.

Hematology Department, University of Ancona, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Torrette di Ancona, Italy. Electronic address:

We prospectively evaluated 2 postconsolidation strategies, administered according to the mobilization outcome, in 72 acute myeloid leukemia (AML) fit elderly patients, achieving complete remission after the first high-dose cytarabine-based induction. Autologous stem cell transplantation (ASCT) was performed in patients collecting ≥3 × 10(6) CD34(+)/kg and low-dose gemtuzumab ozogamicin (GO) was performed in poor mobilizers (collecting <3 × 10(6) CD34(+)/kg). Fifty-five patients (76.3%) underwent peripheral blood stem cell (PBSC) mobilization, after first consolidation, and 24 of 55 (44%) collected >3 × 10(6) CD34(+) cells/kg. Among the 55 patients eligible for PBSC mobilization, 7 did not receive the planned treatment, 23 were allocated for ASCT, and 25 were allocated for GO on an intention-to-treat basis. With a median follow-up of 70 months (range, 24 to 124), 20 of 55 patients are alive, 18 of them in continuous complete remission. The 8-year overall survival (OS) and disease-free survival (DFS) are, respectively, 35.9% (95% confidence interval [CI] 24% to 49.8%) and 31.2% (95% CI, 21% to 43.8%), median OS and DFS were 22 and 16 months, respectively. In multivariate analysis, postconsolidation treatment and hyperleukocytosis (WBC > 50,000/μL) significantly predicted OS and DFS, whereas secondary AML was significantly associated with a higher relapse rate (83.4% versus 54% of de novo AML). Patients with hyperleukocytosis had 0% 3-year OS versus the 46% (at 8 years) in patients without hyperleukocytosis (P = .01); 57% of patients in the GO arm are alive at 8 years, compared with 25.4% of patients in the ASCT arm, who had an overall relative risk (RR) of death of 2.6 (95% CI, 1.2 to 5.8; P = .02). DFS at 8 years was 45.3% in patients receiving GO, compared with 26% in ASCT arm (RR, 2.1; 95% CI, 1 to 4.3; P = .05). Our study outlines low feasibility and efficacy of ASCT in elderly AML patients, whereas postconsolidation with GO appears safe and effective in this unfavorable setting. The study was registered at Umin Clinical Trial Registry (www.umin.ac.jp/ctr), number R000014052.
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http://dx.doi.org/10.1016/j.bbmt.2014.05.019DOI Listing
September 2014

Very low rate of readmission after an early discharge outpatient model for autografting in multiple myeloma patients: an Italian multicenter retrospective study.

Biol Blood Marrow Transplant 2014 Jul 31;20(7):1026-32. Epub 2014 Mar 31.

Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.

We analyzed the main modalities and clinical outcomes of the early discharge outpatient model in autologous stem cell transplantation (EDOM-ASCT) for multiple myeloma in Italy. EDOM-ASCT was employed in 382 patients, for a total of 522 procedures, between 1998 and 2012. Our study showed high homogeneity among centers in terms of inclusion criteria, supportive care, and in hospital readmission criteria. Overall, readmissions during the aplastic phase occurred in 98 of 522 transplantations (18.8%). The major extrahematological complication was neutropenic fever in 161 cases (30.8%), which required readmission in 76 cases. The incidence of severe World Health Organization grade 3 to 4 mucositis was 9.6%. By univariate analysis, fever, mucositis, altered renal function at diagnosis, second transplantation, and transplantation performed late in the course of the disease were significantly correlated with readmission, whereas fever, mucositis, altered renal function, and timing of transplantation remained the only independent predictors by multivariate analysis. Overall, transplantation-related mortality was 1.0%. No center effect was observed in this study (P = .36). The safety and low rate of readmission of the EDOM-ASCT in myeloma trial suggest that this strategy could be extended to other transplantation centers if a stringent patient selection and appropriate management are applied.
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http://dx.doi.org/10.1016/j.bbmt.2014.03.027DOI Listing
July 2014

Factors affecting successful mobilization with plerixafor: an Italian prospective survey in 215 patients with multiple myeloma and lymphoma.

Transfusion 2014 Feb 19;54(2):331-9. Epub 2013 Jun 19.

Section of Hematology and BMT Unit, Cremona Hospital, Cremona, Italy; Department of Hematology and Oncological Sciences, Institute of Hematology "L. & A. Seràgnoli", University of Bologna, Bologna, Italy; Section of Hematology, University Hospital of Ancona, "Ospedali Riuniti", Ancona, Italy; Hemato-Oncology Unit, Istituto Europeo Oncologico, Milan, Italy; Section of Hematology, Reggio Calabria Hospital, Reggio Calabria, Italy; Section of Hematology, University Hospital of Bari, Bari, Italy; Section of Hematology, Tricase Hospital, Tricase, Italy; Section the of Hematology, Rimini Hospital, Rimini, Italy; Section of Hematology, University Hospital Ferrarotto, Policlinico Vittorio Emanuele, Catania, Italy; Section of Hematology, Humanitas Hospital; BMT Unit, S. Raffaele Hospital, Milan, Italy; Section of Hematology, Hospital Casa Sollievo Sofferenza, S. Giovanni Rotondo, Italy; Section of Hematology, Bergamo Hospital, Bergamo, Italy; Section of Hematology and BMT Unit, University Hospital "Careggi", Florence, Italy.

Background: Although the efficacy of plerixafor in peripheral blood stem cell (PBSC) mobilization has been explored in several studies, factors associated with successful plerixafor mobilization after administration of granulocyte-colony-stimulating factor (G-CSF), with or without chemotherapy, have not been investigated. We analyzed data on PBSC mobilization from a large Italian database of lymphoma and myeloma plerixafor-treated patients.

Study Design And Methods: Two endpoints were established to define successful mobilization: patients with at least 2 × 10(6) CD34+ cells/kg collected by three leukapheresis procedures and patients achieving a peak count of at least 20 × 10(6) CD34+ cells/L during mobilization.

Results: Plerixafor achieved successful mobilization in both predicted (n = 64) and proven poor mobilizers (PMs; n = 143), classified according to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) criteria. Successful mobilization was independent of type of mobilization (steady state or chemotherapy); age; sex; disease; number or type of chemotherapy regimens preceding plerixafor; radiation therapy; prior treatment with melphalan, carmustine, lenalidomide, and radioimmune conjugates; and laboratory variables. Multivariate analysis identified previous fludarabine treatment and premobilization platelet count as predictors of successful mobilization.

Conclusion: This large, prospective, nationwide study confirmed plerixafor efficacy for mobilizing PBSCs when added to G-CSF with or without chemotherapy. Plerixafor can overcome negative effects of most predictors of poor mobilization to achieve satisfactory harvest both in predicted and proven PM.
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http://dx.doi.org/10.1111/trf.12265DOI Listing
February 2014

6q deletion detected by fluorescence in situ hybridization using bacterial artificial chromosome in chronic lymphocytic leukemia.

Eur J Haematol 2013 Jul 24;91(1):10-9. Epub 2013 May 24.

SC Ematologia Ospedale C. G. Mazzoni, Ascoli Piceno, Italy.

Deletions of the long arm of chromosome 6 are known to occur at relatively low frequency (3-6%) in chronic lymphocytic leukemia (CLL), and they are more frequently observed in 6q21. Few data have been reported regarding other bands on 6q involved by cytogenetic alterations in CLL. The cytogenetic study was performed in nuclei and metaphases obtained after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin-2. Four bacterial artificial chromosome (BAC) clones mapping regions in bands 6q16, 6q23, 6q25, 6q27 were used as probes for fluorescence in situ hybridization in 107 CLL cases in order to analyze the occurrence and localization of 6q aberrations. We identified 11 cases (10.2%) with 6q deletion of 107 patients studied with CLL. The trends of survival curves and the treatment-free intervals (TFI) of patients with deletion suggest a better outcome than the other cytogenetic risk groups. We observed two subgroups with 6q deletion as the sole anomaly: two cases with 6q16 deletion, and three cases with 6q25.2-27 deletion. There were differences of age, stage, and TFI between both subgroups. By using BAC probes, we observed that 6q deletion has a higher frequency in CLL and is linked with a good prognosis. In addition, it was observed that the deletion in 6q16 appears to be the most frequent and, if present as the only abnormality, it could be associated with a most widespread disease.
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http://dx.doi.org/10.1111/ejh.12115DOI Listing
July 2013

Bortezomib plus dexamethasone followed by escalating donor lymphocyte infusions for patients with multiple myeloma relapsing or progressing after allogeneic stem cell transplantation.

Biol Blood Marrow Transplant 2013 Mar 8;19(3):424-8. Epub 2012 Nov 8.

Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan, Italy.

Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen-identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective.
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http://dx.doi.org/10.1016/j.bbmt.2012.10.032DOI Listing
March 2013

Autologous hematopoietic progenitor cell transplantation for multiple myeloma through an outpatient program.

Expert Opin Biol Ther 2012 Nov 13;12(11):1449-62. Epub 2012 Jul 13.

Divisione di Ematologia con Trapianto di Midollo Osseo e Terapia Intensiva, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.

Introduction: There are considerable concerns regarding the appropriate use of health care resources to reduce costs and waiting lists associated with autologous hematopoietic progenitor cell transplantation (AHPCT). One of the strategies to reach this goal is outpatient-based (OpB) AHPCT.

Areas Covered: We reviewed all the reported experiences in this field and illustrated the various models of OpB AHPCT.

Expert Opinion: The role of high-dose melphalan (HDM) followed by AHPCT in the treatment of Multiple Myeloma (MM) continues to evolve in the novel agent era and the International Myeloma Working Group recommends that AHPCT should be offered at some point in the course of the treatment program for a medically fit patient. The relatively short neutropenia and the limited extra-marrow toxicity after HDM support the hypothesis that MM patients are the most suitable for outpatient transplant programs. Various models have shown that the procedure is feasible and safe and may highly contribute to shorten waiting lists and to considerably cut health costs, with an improvement of quality of life. Ideal candidates may be those who are asymptomatic and fully active, who have a full-time caregiver and who can reside within easy reach from the transplant center.
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http://dx.doi.org/10.1517/14712598.2012.707185DOI Listing
November 2012

Multicenter experience using total lymphoid irradiation and antithymocyte globulin as conditioning for allografting in hematological malignancies.

Biol Blood Marrow Transplant 2012 Oct 5;18(10):1600-7. Epub 2012 Apr 5.

Centro Unico Regionale Trapianti Alberto Neri, A.O. Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects.
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http://dx.doi.org/10.1016/j.bbmt.2012.03.012DOI Listing
October 2012

A new schedule of CHOP/rituximab plus granulocyte-macrophage colony-stimulating factor is an effective rescue for patients with aggressive lymphoma failing autologous stem cell transplantation.

Biol Blood Marrow Transplant 2005 Aug;11(8):627-36

Department of Hematology, University of Ancona, Ancona, Italy.

From 1999 to 2002, 20 patients with aggressive non-Hodgkin lymphoma, among 28 who failed autologous peripheral blood progenitor cell transplantation, were rescued with cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisone (CHOP)/rituximab (RTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). RTX was administered twice during each course of chemotherapy, before CHOP and after GM-CSF. This cytokine was given to increase the antibody-dependent cell-mediated cytotoxicity and to reduce the leukopenia on the basis of our preliminary data, which suggested that this cytokine can upregulate CD20 expression. The relevant (World Health Organization grade 3-4) toxicity mainly consisted of myelosuppression (neutropenia in 60% of patients). Fifteen patients achieved complete remission (CR) or had a partial response, with an overall response rate of 75% (60% CR and 15% partial response). Six of the 12 patients who achieved CR relapsed: 2 died of progressive disease, 1 died of infectious complications after allogeneic transplantation, and 3 are alive in second CR. Eight patients showed progressive disease: 5 died of progressive disease, 1 of secondary acute leukemia, and 1 of infectious complications after allogeneic transplantation, whereas 1 is alive in second CR. At last follow-up, 10 patients are alive, 6 of whom are in complete continuous remission, with a median follow-up of 31 months (range, 3-51 months). The projected 4-year progression-free survival is 31.4%, and the 4-year overall survival is 50%. This new association (RTX, CHOP, and GM-CSF) was feasible in approximately 70% of patients; the overall toxicity was manageable. The good response rate and the promising outcome observed in this subset of patients could be explained by the possible increased synergy between chemotherapy, RTX, and GM-CSF, which should be explored in further studies.
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http://dx.doi.org/10.1016/j.bbmt.2005.05.002DOI Listing
August 2005