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1.
Transplant Cell Ther ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39222792

RESUMO

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant hematology/oncology (n = 8), and radiation oncology (n = 5) from across the United States. Consensus required agreement of ≥75% of participants. Sixteen consensus statements were generated on four topics: (1) criteria for referral for consideration for allo-HCT, (2) allo-HCT preparative regimens and procedures (3) disease status at the time of allo-HCT, and (4) multidisciplinary management in the pre- and post-transplant settings. These clinical practice guidelines provide a framework for decision-making regarding allo-HCT for MF/SS and highlight areas for future prospective investigation.

2.
J Clin Oncol ; 42(19): 2271-2280, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38531001

RESUMO

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/terapia , Doença de Hodgkin/patologia , Doença de Hodgkin/mortalidade , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Prognóstico , Intervalo Livre de Progressão , Estadiamento de Neoplasias
3.
Blood Adv ; 8(1): 130-142, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-37939259

RESUMO

ABSTRACT: In situ vaccination (ISV) triggers an immune response to tumor-associated antigens at 1 tumor site, which can then tackle the disease throughout the body. Here, we report clinical and biological results of a phase 1/2 ISV trial in patients with low-grade lymphoma, combining an intratumoral toll-like receptor 9 (TLR9) agonist with local low-dose radiation and ibrutinib (an inhibitor of B- and T-cell kinases). Adverse events were predominately low grade. The overall response rate was 50%, including 1 complete response. All patients experienced tumor reduction at distant sites. Single-cell analyses of serial fine needle aspirates from injected and uninjected tumors revealed correlates of clinical response, such as lower CD47 and higher major histocompatibility complex class II expression on tumor cells, enhanced T-cell and natural killer cell effector function, and reduced immune suppression from transforming growth factor ß and inhibitory T regulatory 1 cells. Although changes at the local injected site were more pronounced, changes at distant uninjected sites were more often associated with clinical responses. Functional immune response assays and tracking of T-cell receptor sequences provided evidence of treatment-induced tumor-specific T-cell responses. Induction of immune effectors and reversal of negative regulators were both important in producing clinically meaningful tumor responses. The trial was registered at www.clinicaltrials.gov as #NCT02927964.


Assuntos
Linfoma não Hodgkin , Linfoma , Neoplasias , Humanos , Neoplasias/terapia , Linfoma/terapia , Linfoma não Hodgkin/tratamento farmacológico , Adjuvantes Imunológicos , Vacinação , Análise de Célula Única
4.
Pediatr Blood Cancer ; 70(10): e30589, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37486149

RESUMO

PURPOSE/OBJECTIVES: To evaluate dosimetric differences between auto-planned volumetric modulated arc therapy (VMAT) total body irradiation (TBI) technique and two-dimensional radiotherapy using anterior-posterial/posterio-anterial beams (2D AP/PA) TBI technique. METHODS: Ten pediatric patients treated with VMAT-TBI on Varian c-arm linac were included in this study. VMAT-TBI plans were generated using our in-house developed and publicly shared auto-planning scripts. For each VMAT-TBI plan, a 2D AP/PA plan was created replicating the institution's clinical setup with the patient positioned at extended source to skin distance (SSD) with a compensator to account for differences in patient thickness, 50% transmission daily lung blocks, and electron chest wall boosts prescribed to 50% of the photon prescription. Clinically relevant metrics were analyzed and compared between the VMAT and 2D plans. RESULTS: All VMAT-TBI plans achieved planned target volume (PTV) D90% ≥ 100% of prescription. VMAT-TBI PTV D90% significantly increased (7.1% ± 2.9%, p < .001) compared to the 2D technique, whereas no differences were observed in global Dmax (p < .2) and PTV V110% (p < .4). Compared to the 2D plans, significant decreases in the Dmean to the lungs (-25.6% ± 11.5%, p < .001) and lungs-1 cm (-34.1% ± 10.1%, p < .001) were observed with the VMAT plans. The VMAT technique also enabled decrease of dose to other organs: kidneys Dmean (-32.5% ± 5.0%, p < .001) and lenses Dmax (-5.3% ± 8.1%, p = .03); and in addition, for 2 Gy prescription: testes/ovaries Dmean (-41.5% ± 11.5%, p < .001), brain Dmean (-22.6% ± 5.4%, p = .002), and thyroid Dmean (-18.2% ± 16.0%, p = .03). CONCLUSIONS: Superior lung sparing with improved target coverage and similar global Dmax were observed with the VMAT plans as compared to 2D plans. In addition, VMAT-TBI plans provided greater dose reductions in gonads, kidneys, brain, thyroid, and lenses.


Assuntos
Radioterapia de Intensidade Modulada , Humanos , Criança , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Irradiação Corporal Total , Dosagem Radioterapêutica , Órgãos em Risco/efeitos da radiação
5.
Blood ; 141(22): 2727-2737, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36857637

RESUMO

The treatment landscape of relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) has evolved significantly over the past decade after the approval of brentuximab vedotin (BV) and the programmed death-1 (PD-1) inhibitors. We evaluated how outcomes and practice patterns have changed for patients with R/R cHL who underwent autologous hematopoietic cell transplantation (AHCT) at our institution from 2011 to 2020 (N = 183) compared with those from 2001 to 2010 (N = 159) and evaluated prognostic factors for progression-free survival (PFS) and overall survival (OS) in both eras. OS was superior in the modern era with a trend toward lower nonrelapse mortality beyond 2 years after transplant. Among patients who progressed after AHCT, 4-year postprogression survival increased from 43.3% to 71.4% in the modern era, reflecting increasing use of BV and the PD-1 inhibitors. In multivariable analysis for patients that underwent transplant in the modern era, age ≥45 years, primary refractory disease, and lack of complete remission pre-AHCT were associated with inferior PFS, whereas receipt of a PD-1 inhibitor-based regimen pre-AHCT was associated with superior PFS. Extranodal disease at relapse was associated with inferior OS. Our study demonstrates improved survival for R/R cHL after AHCT in the modern era attributed to more effective salvage regimens allowing for better disease control pre-AHCT and improved outcomes for patients who progressed after AHCT. Excellent outcomes were observed with PD-1 inhibitor-based salvage regimens pre-AHCT and support a randomized trial evaluating immunotherapy in the second line setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Humanos , Pessoa de Meia-Idade , Doença de Hodgkin/patologia , Transplante Autólogo , Inibidores de Checkpoint Imunológico/uso terapêutico , Recidiva Local de Neoplasia/terapia , Brentuximab Vedotin/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
6.
EJHaem ; 4(1): 90-99, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36819184

RESUMO

Low-grade lymphomas have a 1%-3% annual risk of transformation to a high-grade histology, and prognostic factors remain undefined. We set to investigate the role of positron emission tomography (PET) metrics in identification of transformation in a retrospective case-control series of patients matched by histology and follow-up time. We measured PET parameters including maximum standard uptake value (SUV-max) and total lesion glycolysis (TLG), and developed a PET feature and lactate dehydrogenase (LDH)-based model to identify transformation status within discovery and validation cohorts. For our discovery cohort, we identified 53 patients with transformation and 53 controls with a similar distribution of follicular lymphoma (FL). Time to transformation and control follow-up time was similar. We observed a significant incremental increase in SUV-max and TLG between control, pretransformation and post-transformation groups (P < 0.05). By multivariable analysis, we identified a significant interaction between SUV-max and TLG such that SUV-max had highest significance for low volume cases (P = 0.04). We developed a scoring model incorporating SUV-max, TLG, and serum LDH with improved identification of transformation (area under the curve [AUC] = 0.91). Our model performed similarly for our validation cohort of 23 patients (AUC = 0.90). With external and prospective validation, our scoring model may provide a specific and noninvasive tool for risk stratification for patients with low-grade lymphoma.

7.
Adv Radiat Oncol ; 8(1): 101071, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36483061

RESUMO

Purpose: Children with leukemia who receive fractionated total body irradiation (fTBI) with 12 to 13.2 Gy as part of conditioning for hematopoietic stem cell transplant are frequently treated with an additional 4 Gy testicular boost to reduce the risk of testicular relapse. While institutional practices vary, limited data exists regarding whether the 4-Gy testicular boost reduces the risk of relapse and whether it causes toxicity beyond that imparted by TBI. This study compared the survival and endocrine outcomes among the patients who were treated with and without a testicular boost as part of fTBI from 1990 to 2019 at our center. Methods and Materials: We retrospectively reviewed charts of male children with leukemia treated with fTBI as part of a conditioning regimen for stem cell transplant from 1990 to 2019. Reported outcomes included progression-free survival, testicular relapse rate, and overall survival. Gonadal dysfunction and fertility were assessed by comparing the rate of abnormally low testosterone or high luteinizing hormone or follicular stimulating hormone, number of offspring, fertility service use, and abnormal sperm count in the subsequent follow-up period between the testicular boost and nonboost subset. Results: Ninety-three male patients (63 acute lymphoblastic leukemia, 30 acute myeloid leukemia) with a median age of 9 years (range, 1-22) and follow-up of 3.3 years were included. In addition to 12- to 13.2-Gy fTBI, 51 male patients (54%) received a testicular boost to 4 Gy. There was 1 testicular relapse in the boost subset and none in the nonboost subset. Five-year progression-free survival for the boost and nonboost subset was 74% and 66%, respectively (P = .31). On multivariable analysis, boost was not associated with improved relapse-free survival or overall survival. More patients in the boost subset (35 of 51, 69%) had abnormal serum gonadal blood work compared with the nonboost subset (18 of 42, 43%) (P = .03). Conclusions: Omission of testicular boost may be associated with comparable oncologic but improved gonadal endocrine outcomes and should be further studied.

8.
Cancer Invest ; : 1-8, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33899635

RESUMO

We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34 Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the four extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5 months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

9.
Pediatr Blood Cancer ; 69(6): e29689, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35373904

RESUMO

INTRODUCTION: Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy total body irradiation (VMAT-TBI). METHODS: We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019 to 2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. RESULTS: Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with nonmyeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs Dmean was 7.3 ± 0.3 Gy for myeloablative regimens (range: 6.8-7.8). Kidneys were spared to average mean dose of 71.4 ± 4.8% of prescription dose. Gonadal sparing was achieved for patients treated for nonmalignant diseases to Dmean of 0.7 ± 0.1 Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI. CONCLUSION: VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Radioterapia de Intensidade Modulada , Adolescente , Criança , Humanos , Recidiva Local de Neoplasia/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Irradiação Corporal Total/métodos , Adulto Jovem
10.
J Natl Compr Canc Netw ; 20(4): 322-334, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35390768

RESUMO

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.


Assuntos
Doença de Hodgkin , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/radioterapia , Humanos
11.
J Natl Compr Canc Netw ; 20(3): 285-308, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35276674

RESUMO

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.


Assuntos
Linfadenopatia Imunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/patologia , Linfadenopatia Imunoblástica/terapia , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia
12.
Pract Radiat Oncol ; 12(3): 245-258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35182803

RESUMO

PURPOSE: In this article, we describe the technical aspects of the Stanford volumetric modulated arc therapy (VMAT) total body irradiation (TBI) technique, compare it with other VMAT-TBI techniques, and share our initial experience. METHODS AND MATERIALS: From September 2019 to August 2021, 35 patients were treated with VMAT-TBI at our institution. Treatment planning was performed using in-house developed automated planning scripts. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses) and nonmyeloablative with benign disease (lungs, kidneys, lenses, gonads, brain, and thyroid). Quality assurance was performed using electronic portal imaging device portal dosimetry and Mobius3D. Robustness was evaluated for the first 10 patients by performing local and global isocenter shifts of 5 mm. Treatment was delivered using image-guided radiation therapy for every isocenter and every fraction. In vivo measurements were performed on the match line between the VMAT and anterior-posterior/posterior-anterior fields and on the testes for the first fraction. RESULTS: The lungs, lungs - 1 cm, and kidneys Dmean were consistently spared to 57.6% ± 4.4%, 40.7% ± 5.5%, and 70.0% ± 9.9% of the prescription dose, respectively. Gonadal sparing (Dmean = 0.69 ± 0.13 Gy) was performed for all patients with benign disease. The average planning target volume (PTV) maximum dose to 1 cubic centimeter (D1cc) was 120.7% ± 6.4% for all patients. The average Gamma passing rate for the VMAT plans was 98.1% ± 1.6% (criterion of 3%/2 mm). Minimal differences were observed between Mobius3D- and Eclipse AAA-calculated PTV Dmean (0.0% ± 0.3%) and lungs Dmean (-2.5% ± 1.2%). Robustness evaluation showed that the PTV Dmax and lungs Dmean were insensitive to small positioning deviations between the VMAT isocenters (1.1% ± 2.4% and 1.2% ± 1.0%, respectively). The average match-line dose measurement indicated patient setup was reproducible (96.1% ± 4.5% relative to prescription dose). Treatment time, including patient setup and beam-on, was 47.5 ± 9.5 min. CONCLUSIONS: The Stanford VMAT-TBI technique, from simulation to treatment delivery, was presented and compared with other VMAT-TBI techniques. Together with publicly shared autoplanning scripts, our technique may provide the gateway for wider adaptation of this technology and the possibility of multi-institutional studies in the cooperative group setting.


Assuntos
Radioterapia de Intensidade Modulada , Humanos , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Irradiação Corporal Total/métodos
14.
Artigo em Inglês | MEDLINE | ID: mdl-33997322

RESUMO

•Techniques for non-lead scalp-shielding in total skin therapy are lacking.•3D-printing is a promising technique for patient-specific conformal shielding.•We present a case of effective scalp shielding with 3D-printing.

15.
J Clin Oncol ; 39(20): 2257-2265, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-33909449

RESUMO

PURPOSE: To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavorable-risk Hodgkin lymphoma. METHODS: In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4-negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavorable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4. RESULTS: Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering-defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall 2-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the 2-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8%), and peripheral neuropathy (54%), which was largely reversible. CONCLUSION: BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4-negative patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Quimiorradioterapia , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Dacarbazina/uso terapêutico , Progressão da Doença , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos , Vimblastina/uso terapêutico , Adulto Jovem
16.
Adv Radiat Oncol ; 6(3): 100629, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748543

RESUMO

PURPOSE: Management of patients with refractory mycosis fungoides and Sézary syndrome (SS) is often challenging, as available therapies lack durable response and consistent activity across disease compartments. Combining low-dose total skin electron beam therapy (LD-TSEBT) upfront with mogamulizumab could optimize the clinical outcome of these patients. LD-TSEBT is effective in clearing skin disease, and mogamulizumab is an antitumor immunotherapy with long-term tolerability, suggesting its potential as a maintenance therapy after maximal response. We examine the combination regimen in patients with SS who were previously treated. METHODS AND MATERIALS: Two patients with SS were treated with combination LD-TSEBT and mogamulizumab. Both patients received mogamulizumab 1 mg/kg weekly × 4 and then bi-weekly; LD-TSEBT (12 Gy) was initiated within 2 days of starting mogamulizumab and given over 2-3 weeks. Safety and clinical response were evaluated. RESULTS: Total skin electron beam therapy plus mogamulizumab (TSE-Moga) was well-tolerated without any unanticipated adverse events. Patient 1 (T4N2bM0B2) was a 63-year-old woman with 4 prior systemic therapies; time to global response with TSE-Moga was 9 weeks. Patient 2 (T4NxM0B2) was a 75-year-old man with 5 prior systemic therapies; time to global response was 4 weeks. Both patients lacked global response to their prior therapies but achieved global complete response (blood and skin) with TSE-Moga. After a follow-up of 72 weeks and 43 weeks, respectively, global complete response continued. CONCLUSIONS: TSE-Moga demonstrated excellent tolerability and promising clinical activity with ongoing global complete responses in 2 patients with refractory SS. This encouraging experience supports our ongoing clinical trial evaluating the efficacy and safety of TSE-Moga in mycosis fungoides and SS.

17.
Leuk Lymphoma ; 62(8): 1840-1849, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33622155

RESUMO

We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7 years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0-1 (smIPI, 58.1%), and had non-bulky disease (<7 cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0-1 versus 2-4 was 89.5% versus 69.7%, respectively (P = 0.005). Bulky disease (≥7 cm) was associated with worse PFS and OS on univariable and multivariable analyses (P < 0.05). Patients with smIPI 0-1 without bulky disease have excellent outcomes. However, patients with smIPI 2-4 or bulky disease have a high risk of progression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
18.
Int J Radiat Oncol Biol Phys ; 110(2): 444-451, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385495

RESUMO

PURPOSE: Combined modality therapy (CMT) is standard therapy for early-stage Hodgkin lymphoma (ESHL). We previously reported excellent outcomes with the abbreviated Stanford V regimen. Herein we report updated results with median follow-up >10 years on survival, therapy-related late effects, and impact of disease risk factors on patient outcomes. METHODS AND MATERIALS: The G4 and G5 studies enrolled patients with stage I-IIA nonbulky ESHL. Patients received 8 weeks of Stanford V chemotherapy followed by 30 Gy modified involved-field radiation therapy (mIFRT) (G4) or Stanford V-C + 20 Gy mIFRT (G5). Patients were categorized as favorable or unfavorable risk per German Hodgkin Study Group (GHSG) criteria and outcomes between groups compared. RESULTS: A total of 129 patients were enrolled (68 favorable and 61 unfavorable risk). In the G4 study (n = 87), at median follow-up of 19.7 years, 5-, 10-, and 15-year progression-free survival (PFS) and overall survival (OS) were 95.4%/97.7%, 91.8%/96.5%, and 91.8%/95.3%, respectively. In the G5 study (n = 42), at median follow-up of 13.5 years, the 5-, 10-, and 15-year PFS and OS were 92.9%/100%, 92.9%/100%, and 88.4%/91.9%, respectively. PFS (P = .86) and OS (P = .86) were not significantly different between studies. There were also no significant differences between studies in patients with favorable or unfavorable risk for PFS (F: P = .53; U: P = .96), OS (F: P = .99; U: P = .78), secondary malignancies (F: P = .74; U: P = 1.0), and cardiovascular complications (F: no cases; U: P = 1.0). CONCLUSIONS: The G4 and G5 studies achieve high rates of durable remission; 20 versus 30 Gy mIFRT and cyclophosphamide substituted for mechlorethamine did not compromise nodal control, PFS, or OS in both favorable and unfavorable risk disease. These results support the efficacy of CMT in early-stage disease and lower-dose radiation therapy in patients with favorable and nonbulky unfavorable ESHL.


Assuntos
Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Terapia Combinada/métodos , Ciclofosfamida/uso terapêutico , Substituição de Medicamentos , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Mecloretamina/uso terapêutico , Pessoa de Meia-Idade , Segunda Neoplasia Primária , Intervalo Livre de Progressão , Dosagem Radioterapêutica , Indução de Remissão , Fatores de Risco , Terapia de Salvação/métodos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Pract Radiat Oncol ; 11(2): e134-e138, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32795616

RESUMO

Reproductive toxicity is common after total body irradiation (TBI) and has major quality of life implications for patients. In that context, this is the first report of gonadal-sparing volumetric-modulated arc therapy (VMAT) TBI, successfully delivered in a boy and a girl with aplastic anemia. Both patients' VMAT TBI plans demonstrated improved gonadal sparing versus simulated conventional 2-dimensional (2D) approach (mean testes dose, 0.45 Gy VMAT vs 0.72 Gy 2D; mean ovary dose, 0.64 Gy VMAT vs 1.47 Gy 2D). Planning target volume coverage was also improved for both cases with the VMAT plan versus conventional 2D plan (2 Gy D90% vs 1.9 Gy D90%, respectively). Given these dosimetric advantages, the present study can serve as a proof-of-concept for further prospective studies evaluating this technique for wider applications in populations receiving TBI.


Assuntos
Radioterapia de Intensidade Modulada , Irradiação Corporal Total , Feminino , Humanos , Masculino , Órgãos em Risco , Estudos Prospectivos , Qualidade de Vida , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos
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