Publications by authors named "Lavinia Grapulin"

13 Publications

  • Page 1 of 1

HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia.

Blood Adv 2021 Mar;5(5):1333-1339

Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS) Bambino Gesù Children's Hospital, Rome, Italy.

We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation (HSCT) in the context of a prospective, single-center phase 2 trial. Sustained primary engraftment was achieved in 22 (91.6%) of 24 patients, with median time to neutrophil recovery of 12 days (range, 9-15 days) and platelet recovery of 10 days (range, 7-14 days). Cumulative incidences of grade 1 to 2 acute graft-versus-host disease (GVHD) and chronic GVHD were 17.4% (95% confidence interval [CI], 5.5%-35.5%) and 5.5% (95% CI, 0.8%-33.4%), respectively. The conditioning regimen, which included fludarabine, low-dose cyclophosphamide and, in most patients, single-dose irradiation was well tolerated; no fatal transplant-related toxicity was observed. With a median follow-up of 5.2 years (range, 0.3-8.7 years), the overall and event-free survival probabilities were 100% and 86.3% (95% CI, 62.8%-95.4%), respectively (2 graft failures and 1 case of poor graft function were considered as events). The 2 patients who experienced primary graft failure underwent a subsequent successful HSCT from the other parent. This is the first report of FA patients given TCRαβ+/CD19+-depleted haplo-HSCT in the context of a prospective trial, and the largest series of T-cell-depleted haplo-HSCT in FA reported to date. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
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http://dx.doi.org/10.1182/bloodadvances.2020003707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948273PMC
March 2021

Immune Modulation Properties of Zoledronic Acid on TcRγδ T-Lymphocytes After TcRαβ/CD19-Depleted Haploidentical Stem Cell Transplantation: An analysis on 46 Pediatric Patients Affected by Acute Leukemia.

Front Immunol 2020 12;11:699. Epub 2020 May 12.

Department of Pediatric Hematology and Oncology and of Cell and Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS), Bambino Gesù Childrens' Hospital, Rome, Italy.

TcRαβ/CD19-cell depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a promising new platform for children affected by acute leukemia in need of an allograft and lacking a matched donor, disease recurrence being the main cause of treatment failure. The use of zoledronic acid to enhance TcRγδ+ lymphocyte function after TcRαβ/CD19-cell depleted haplo-HSCT was tested in an open-label, feasibility, proof-of-principle study. Forty-six children affected by high-risk acute leukemia underwent haplo-HSCT after removal of TcRαβ+ and CD19+ B lymphocytes. No post-transplant pharmacological graft-versus-host disease (GvHD) prophylaxis was given. Zoledronic acid was administered monthly at a dose of 0.05 mg/kg/dose (maximum dose 4 mg), starting from day +20 after transplantation. A total of 139 infusions were administered, with a mean of 3 infusions per patient. No severe adverse event was observed. Common side effects were represented by asymptomatic hypocalcemia and acute phase reactions (including fever, chills, malaise, and/or arthralgia) within 24-48 h from zoledronic acid infusion. The cumulative incidence of acute and chronic GvHD was 17.3% (all grade I-II) and 4.8% (all limited), respectively. Patients given 3 or more infusions of zoledronic acid had a lower incidence of both acute GvHD (8.8 vs. 41.6%, = 0.015) and chronic GvHD (0 vs. 22.2%, = 0.006). Transplant-related mortality (TRM) and relapse incidence at 3 years were 4.3 and 30.4%, respectively. Patients receiving repeated infusions of zoledronic acid had a lower TRM as compared to those receiving 1 or 2 administration of the drug (0 vs. 16.7%, = 0.01). Five-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 67.2 and 65.2%, respectively, with a trend toward a better OS for patients receiving 3 or more infusions (73.1 vs. 50.0%, = 0.05). The probability of GvHD/relapse-free survival was significantly worse in patients receiving 1-2 infusions of zoledonic acid than in those given ≥3 infusions (33.3 vs. 70.6%, respectively, = 0.006). Multivariable analysis showed an independent positive effect on outcome given by repeated infusions of zoledronic acid (HR 0.27, = 0.03). These data indicate that the use of zoledronic acid after TcRαβ/CD19-cell depleted haploHSCT is safe and may result in a lower incidence of acute GvHD, chronic GvHD, and TRM.
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http://dx.doi.org/10.3389/fimmu.2020.00699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235359PMC
March 2021

Minimal residual disease monitoring in early stage follicular lymphoma can predict prognosis and drive treatment with rituximab after radiotherapy.

Br J Haematol 2020 01 5;188(2):249-258. Epub 2019 Aug 5.

Haematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.

Since 2000, we have investigated 67 consecutive patients with stage I/II follicular lymphoma (FL) for the presence of BCL2/IGH rearrangements by polymerase chain reaction (PCR), real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR). All patients were treated with involved-field radiotherapy (IF-RT) (24-30 Gy). From 2005, patients with minimal residual disease (MRD) after IF-RT received rituximab (R) (375 mg/m , 4 weekly administrations). The median follow-up is 82 months (17-196). At diagnosis, 72% of patients were BCL2/IGH+. Progression-free survival (PFS) was significantly better in patients with undetectable/low levels (<10 ) of circulating BCL2/IGH+ cells at diagnosis and in those who were persistently MRD- during follow-up (P = 0·0038). IF-RT induced an MRD- status in 50% of cases; 16/19 (84%) MRD+ patients after IF-RT became MRD- after R treatment. A significantly longer PFS was observed in MRD+ patients treated with R compared to untreated MRD+ patients (P = 0·049). In early stage FL, both circulating levels of BCL2/IGH+ cells at diagnosis and MRD status during follow-up bear prognostic implications. Standard IF-RT fails to induce an MRD-negative status in half of patients. Most patients become MRD- following treatment with R and this is associated with a significantly better PFS.
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http://dx.doi.org/10.1111/bjh.16125DOI Listing
January 2020

Radiation therapy in indolent primary cutaneous B cell lymphoma: a single institute experience.

Ann Hematol 2018 Dec 10;97(12):2411-2416. Epub 2018 Aug 10.

Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of Rome, Viale Regina Elena 326, 00161, Rome, Italy.

To report the clinical results after definitive radiotherapy (RT) for indolent primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients treated for indolent pcBCL with RT with a curative intent between 1992 and 2012 were reviewed. All cases were (re)classified according to the World Health Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with RT resulted in complete response (CR) in all patients. Eight patients showed one or multiple relapses confined to the skin. No in-field recurrences were observed. For the entire cohort, the 10-year relapse-free survival (RFS) and overall survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients with trunk lesion was 89.4% versus 66.9% for those with other location (p = 0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple lesions (p = 0.04). An excellent survival can be achieved with definitive RT in indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions probably warrants intensification of therapy. Prospective studies are mandatory.
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http://dx.doi.org/10.1007/s00277-018-3471-xDOI Listing
December 2018

Radiotherapy in indolent primary cutaneous B-cell lymphoma.

Hematol Oncol 2018 Jun 3. Epub 2018 Jun 3.

Department of Radiotherapy, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1002/hon.2518DOI Listing
June 2018

Head and neck diffuse large B cell lymphomas (HN-DLBCL) in human immunodeficiency virus (HIV) positive patients: long-term results in the highly active antiretroviral therapy (HAART) era.

Eur Arch Otorhinolaryngol 2017 Oct 12;274(10):3735-3739. Epub 2017 Jul 12.

Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161, Rome, Italy.

To report long-term outcomes and toxicity rates after chemotherapy (CHT) followed by radiotherapy (RT) in the highly active antiretroviral therapy (HAART) era in human immunodeficiency virus (HIV) positive patients with head and neck diffuse large B cell lymphomas (HN-DLBCL). Clinical data concerning consecutive HIV patients treated for DLBCL located in head and neck region with CHT and RT were retrospectively reviewed. Systemic treatment consisted of combination CHT agents given with concomitant HAART and regimen was left to oncologists' discretion. Involved field RT was delivered at a total dose of 30-36 Gy (2 Gy per fraction). Survival rates were estimated using the Kaplan-Meier method. Toxicity was evaluated using National Cancer Institute's Common Terminology Criteria for Adverse Events. Overall, 13 patients were included. There were no missing data. Eight patients had advanced disease (stage III-IV = 8; 61.5%). The most common primary tumor location was oral cavity (n = 7) with large mass at presentation. All patients completed the programmed treatment. Severe acute toxicity was observed in one patient, only. Overall, three patients had died and no treatment-related deaths occurred. After a median follow-up of 152 months, the 20-year overall survival and disease-free survival rates were 65.9 and 41.5%, respectively. Globally, there were no RT-related late complications. This data analysis suggested that CHT followed by RT can be safety proposed in the management of patients with HIV-related HN-DLBCL in the HAART era. Further investigations are necessary to validate our results.
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http://dx.doi.org/10.1007/s00405-017-4672-yDOI Listing
October 2017

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion.

Blood 2017 08 6;130(5):677-685. Epub 2017 Jun 6.

Immunology Research Area, IRCCS Ospedale Bambino Gesù, Rome, Italy.

Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. We developed a novel method of graft manipulation based on negative depletion of αβ T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. Eighty AL children, transplanted between September 2011 and September 2014, were enrolled in the trial. All children were given a fully myeloablative preparative regimen. Anti-T-lymphocyte globulin from day -5 to -3 was used for preventing graft rejection and graft-versus-host disease (GVHD); no patient received any posttransplantation GVHD prophylaxis. Two children experienced primary graft failure. The cumulative incidence of skin-only, grade 1-2 acute GVHD was 30%; no patient developed extensive chronic GVHD. Four patients died, the cumulative incidence of nonrelapse mortality being 5%, whereas 19 relapsed, resulting in a 24% cumulative incidence of relapse. With a median follow-up of 46 months for surviving patients, the 5-year probability of chronic GVHD-free, relapse-free survival (GRFS) is 71%. Total body irradiation-containing preparative regimen was the only variable favorably influencing relapse incidence and GRFS. The outcomes of these 80 patients are comparable to those of 41 and 51 children given transplantation from an HLA-identical sibling or a 10/10 allelic-matched unrelated donor in the same period. These data indicate that haplo-HSCT after αβ T- and B-cell depletion represents a competitive alternative for children with AL in need of urgent allograft. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
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http://dx.doi.org/10.1182/blood-2017-04-779769DOI Listing
August 2017

Second cancer incidence in primary mediastinal B-cell lymphoma treated with methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin regimen with or without rituximab and mediastinal radiotherapy: Results from a monoinstitutional cohort analysis of long-term survivors.

Hematol Oncol 2017 Dec 12;35(4):554-560. Epub 2017 Jan 12.

Department of Cellular Biotechnologies and Hematology, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.

Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.
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http://dx.doi.org/10.1002/hon.2377DOI Listing
December 2017

Treatment Complications and Long-term Outcomes of Total Body Irradiation in Patients with Acute Lymphoblastic Leukemia: A Single Institute Experience.

Anticancer Res 2016 09;36(9):4859-64

Department of Radiotherapy, Thrombosis Center, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy Spencer-Lorillard Foundation, Rome, Italy.

Background: The aim of this study was to evaluate treatment-related toxicity and clinical outcomes of total body irradiation (TBI) in patients with acute lymphoblastic leukemia (ALL).

Patients And Methods: We performed a retrospective review of all patients with ALL who underwent TBI-based conditioning regimen at our Institution between 2000 and 2012.

Results: A total of 211 patients were included. The median follow-up was 40 months. The 5-year overall survival and disease-free survival were 64.7% and 62.8%, respectively. The 5-year overall survival rate for the 163 children was 67.6% (95% confidence interval=55-77%). Disease status at time of transplant did not improve disease-free survival. Gastrointestinal acute toxicity was the most common early side-effect (19.9%). Acute graft-versus-host disease was reported in 31 patients (14.7%). Main late toxicities were cataract induction (12.8%) and growth, gonadal and endocrine effects (36%).

Conclusion: TBI-based conditioning regimen led to a high survival rate with remarkably low radiation-related toxicity, suggesting that TBI provides a feasible therapeutic option in patients with ALL.
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http://dx.doi.org/10.21873/anticanres.11049DOI Listing
September 2016

An unusual case of fatty liver in a patient with desmoid tumor.

World J Gastroenterol 2012 Jun;18(24):3173-6

Department of Radiological Sciences-Oncology and Pathological Anatomy, and Department of Radiotherapy, University of Rome "La Sapienza", 00161 Rome, Italy.

A desmoid tumor, also known as aggressive fibromatosis, is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues. It can occur in any anatomical location, most commonly the abdominal wall, shoulder girdle and retroperitoneum. The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures. It is associated with a high local recurrence rate after resection. Many issues regarding the optimal treatment of desmoid tumors remain controversial. Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life. Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions. Desmoid tumors tend to be locally infiltrative, therefore, the fields must be generous to prevent marginal recurrence. The radiation dose appropriate for treating desmoid tumors remains controversial. We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection, treated with radiotherapy. The patient achieved complete tumor regression at 4 mo after radiotherapy, and he is clinically free of disease at 12 mo after the end of treatment, with an acceptable quality of life. The patient developed short bowel syndrome as a complication of second surgical resection. Consequently, radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.
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http://dx.doi.org/10.3748/wjg.v18.i24.3173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386332PMC
June 2012

Efficacy of the BEACOPP regimen in refractory and relapsed Hodgkin lymphoma.

Leuk Lymphoma 2009 Nov;50(11):1803-8

Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.

The BEACOPP regimen is a consolidated first-line treatment regimen for advanced stage Hodgkin lymphoma (HL), while few data are available on the efficacy of this regimen in advanced disease. About 50% of patients with HL relapsed after or refractory to first-line therapy achieve a durable response after peripheral blood stem cell transplantation (PBSCT). Patients relapsing after a PBSCT (performed as second line therapy) have a very poor prognosis. We evaluated the efficacy of BEACOPP in two settings: patients refractory or in relapse after first-line therapy (Group A) and patients relapsing after a PBSCT (Group B). Twenty-three patients with HL, admitted between February 2003 and April 2007, were retrospectively studied: 10 patients in Group A and 13 in Group B. Group A: Nine complete remissions (CR) and one partial remission (PR) were achieved following BEACOPP treatment. After a median follow-up of 32 months, one patient has died due to secondary leukemia, while the other eight are alive, five (50%) in second CR, three in third CR after PBSCT and one with disease. Group B: Eight of the 13 patients (62%) obtained a CR, one patient a PR, two were refractory and two have died of toxicity. To date, eight patients (62%) are alive, four (31%) still in CR. All patients experienced hematologic toxicity (WHO 3-4) with two deaths due to septic shock. These results show that BEACOPP is an effective regimen for both refractory/relapsed patients with HL after first-line treatment (Group A) and for patients relapsing after a PBSCT (Group B) with a 3-year probability of overall survival, progression-free survival, and cumulative incidence of relapse of 90, 50, and 33.3% in Group A, and 61, 31, and 37.5% in Group B, respectively.
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http://dx.doi.org/10.3109/10428190903254383DOI Listing
November 2009

MACOP-B and involved-field radiotherapy is an effective and safe therapy for primary mediastinal large B cell lymphoma.

Int J Radiat Oncol Biol Phys 2008 Nov 9;72(4):1154-60. Epub 2008 May 9.

Department of Radiation and Radiotherapy, University of Rome La Sapienza, Rome, Italy.

Purpose: To report the clinical findings and long-term results of front-line, third-generation MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) chemotherapy and mediastinal involved-field radiotherapy (IFRT) in 85 consecutive, previously untreated patients with primary mediastinal large B cell lymphoma (PMLBCL) diagnosed and managed at a single institution.

Methods And Materials: Between 1991 and April 2004, 92 consecutive, untreated patients with PMLBCL were treated at our institution. The median age was 33 years (range, 15-61 years), 46 patients (50%) showed a mediastinal syndrome at onset; 52 patients (57%) showed a low/low-intermediate (0 to 1) and 40 patients (43%) an intermediate-high/high (2 to 3) International Prognostic Index (IPI) score. Eighty-five patients were treated with standard chemotherapy (MACOP-B), and 80 underwent mediastinal IFRT at a dose of 30-36 Gy.

Results: After a MACOP-B regimen, the overall response rate was 87% and the partial response rate 9%. After chemotherapy, (67)Ga scintigraphy/positron emission tomography results were positive in 43 of 52 patients (83%), whereas after IFRT 11 of 52 patients (21%) remained positive (p < 0.0001). After a median follow-up of 81 months (range, 2-196 months), progression or relapse was observed in 15 of 84 patients (18%). The projected 5-year overall survival and progression-free survival rates were 87% and 81%, respectively. The 5-year overall survival and progression-free survival rates were better for patients with an IPI of 0 to 1 than for those with an IPI of 2 to 3 (96% vs. 73% [p = 0.002] and 90% vs. 67% [p = 0.007], respectively).

Conclusions: Combined-modality treatment with intensive chemotherapy plus mediastinal IFRT induces high response and lymphoma-free survival rates. Involved-field RT plays an important role in inducing negative results on (67)Ga scintigraphy/positron emission tomography in patients responsive to chemotherapy.
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http://dx.doi.org/10.1016/j.ijrobp.2008.02.036DOI Listing
November 2008

Feasibility and results of a multimodality approach in elderly patients with localized intermediate to high-grade non-Hodgkin's lymphomas.

Tumori 2004 May-Jun;90(3):289-93

Radioterapia Oncologica, Dipartimento di Radiologia, University of Rome La Sapienza, Italy.

Aims And Background: A prospective clinical study to determine efficacy and feasibility of a brief course or standard course of anthracycline-based chemotherapy and consolidation radiation therapy in non-Hodgkin's lymphoma patients over 60 years of age.

Methods: Twenty-five consecutive patients with stage I-IE intermediate to high-grade non-Hodgkin's lymphoma aged 60 and older were treated in an outpatient setting in the Radiotherapy Oncology and Hematology units. All patients had a performance status of 0-1 according to WHO criteria. The survival end points, ie, overall survival, disease-free survival and event-free survival, were considered. Lactate dehydrogenase value, nodal versus extranodal localization and dose intensity were assessed as risk factors for disease-free and overall survival. A comparison using logrank analysis with a well-matched group of stage I-IE non-Hodgkin's lymphoma patients aged less than 60 years was performed.

Results: The 5-year overall and disease-free survival rates were 90% and 86%, respectively. There was no statistical difference with respect to the younger population regarding these survival end points. Finally, the 5-year event-free survival was 85% and 86% for elderly and younger patients, respectively, without statistical difference (P = 0.41). Neither acute nor late toxicity (G3-G4) was observed during chemotherapy and radiotherapy treatment and the follow-up in the elderly group.

Conclusions: We confirm the efficacy and feasibility of a full-dose combined chemoradiotherapy in elderly patients with a good performance status with localized I-IE intermediate to high-grade non-Hodgkin's lymphoma.
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August 2004