GRACIA APARECIDA MARTINEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
15 resultados
Resultados de Busca
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- Is it feasible to use granulocyte-colony stimulating factor alone to mobilize progenitor cells in multiple myeloma patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen?(2016) CRUSOE, Edvan de Queiroz; HIGASHI, Fabiana; MARTINEZ, Gracia Aparecida; BARROS, José Carlos; BELLESSO, Marcelo; ROSSATO, Marina; MARRET, Ana Cinira F.; CHIATTONE, Carlos Sérgio; HUNGRIA, Vania Tietsch de MoraesABSTRACT Background: Cyclophosphamide plus thalidomide as induction for multiple myeloma patients eligible for autologous stem cell transplantation may be a limiting factor for cell mobilization. The minimum acceptable mobilized peripheral blood stem cell count to prevent deleterious effects during transplantation is 2.0 × 106 CD34+ cells/kg. Combining other treatments to granulocyte-colony stimulating factor, such as cyclophosphamide, could overcome the mobilization limitation. The objective of this study was to assess the number of CD34+ cells mobilized using granulocyte-colony stimulating factor with and without cyclophosphamide after induction with cyclophosphamide, thalidomide and dexamethasone. Methods: A retrospective study was performed of a cohort of multiple myeloma patients submitted to autologous stem cell transplantations at two Brazilian centers between May 2009 and July 2013. The oral cyclophosphamide and thalidomide induction doses used were 1500 mg/month and 100-200 mg/day, respectively. Mobilization doses were 10-15 mcg/kg granulocyte-colony stimulating factor with 2-4 g/m2 cyclophosphamide, or 15-20 mcg/kg granulocyte-colony stimulating factor alone for 5 days. Collection of >2.0 × 106 CD34+ cells/kg was considered sufficient. Results: Eighty-eight patients were analyzed; only 18 received cyclophosphamide. The median age was 58 years old (range: 51-62) for the granulocyte-colony stimulating factor group and 56.5 years old (range: 54-60) for granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3, respectively. The group that received cyclophosphamide collected a higher median number of progenitor cells [3.8 (range: 3.1-4.4) vs. 3.2 (range: 2.3-3.8)] (p-value = 0.008). No correlation was observed between better responses or number of induction cycles and the number of cells collected. Conclusion: The number of cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide was higher. However, in both groups, the median number of CD34+ cells was sufficient to perform a single autologous stem cell transplantation; no deleterious effects were reported during harvesting.
- CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: Case report(2014) VASCONCELOS, Dewton de Moraes; BEITLER, Beatriz; MARTINEZ, Gracia A.; PEREIRA, Juliana; AMIGO FILHO, Jose Ulysses; KLAUTAU, Giselle Burlamaqui; LIAN, Yu Cheng; NEGRA, Marinella Della; DUARTE, Alberto Jose da SilvaLeukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells. (C) 2014 Published by Elsevier Inc.
- Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study(2023) MARTIN, Thomas; DIMOPOULOS, Meletios-Athanasios; MIKHAEL, Joseph; YONG, Kwee; CAPRA, Marcelo; FACON, Thierry; HAJEK, Roman; SPICKA, Ivan; BAKER, Ross; KIM, Kihyun; MARTINEZ, Gracia; MIN, Chang-Ki; POUR, Ludek; LELEU, Xavier; ORIOL, Albert; KOH, Youngil; SUZUKI, Kenshi; CASCA, France; MACE, Sandrine; RISSE, Marie-Laure; MOREAU, PhilippeLonger-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 trial IKEMA (NCT03275285), in a prespecified, follow-up analysis of progression-free survival (PFS, primary study endpoint), final complete response (CR) using Hydrashift Isa immunofixation assay, minimal residual disease (MRD) negativity, and safety. Enrolled patients had relapsed/refractory multiple myeloma (1-3 prior treatment lines). Isa 10 mg/kg was administered intravenously weekly in cycle 1 then biweekly. Efficacy analyses were performed in the intent-to-treat population (Isa-Kd: n = 179, Kd: n = 123) and safety evaluated in treated patients (Isa-Kd: n = 177, Kd: n = 122). Consistent with the primary interim analysis, the addition of Isa to Kd prolonged PFS (HR 0.58, 95.4% CI: 0.42-0.79; median PFS 35.7 [95% CI: 25.8-44.0] vs 19.2 [95% CI: 15.8-25.0] months). PFS benefit was observed with Isa-Kd across subgroups, including patients with poor prognosis. The stringent CR/CR rate was 44.1% vs 28.5% (odds-ratio: 2.09, 95% CI: 1.26-3.48), the MRD negativity rate 33.5% vs 15.4% (odds-ratio: 2.78, 95% CI: 1.55-4.99) and the MRD negativity CR rate 26.3% vs 12.2%, with Isa-Kd vs Kd. The safety profile of Isa-Kd was similar to that reported in the prior interim analysis. These findings further support Isa-Kd as a standard-of-care treatment for relapsed multiple myeloma patients.
- Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial(2021) MOREAU, Philippe; DIMOPOULOS, Meletios-Athanasios; MIKHAEL, Joseph; YONG, Kwee; CAPRA, Marcelo; FACON, Thierry; HAJEK, Roman; SPICKA, Ivan; BAKER, Ross; KIM, Kihyun; MARTINEZ, Gracia; MIN, Chang-Ki; POUR, Ludek; LELEU, Xavier; ORIOL, Albert; KOH, Youngil; SUZUKI, Kenshi; RISSE, Marie-Laure; ASSET, Gaelle; MACE, Sandrine; MARTIN, ThomasBackground Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, openlabel study compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple rnyeloma. Methods This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple rnyelorna aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received time approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285. Findings Between Nov 15,2017, and March 21,2019,302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19.15 months (95% CI 15.77-not reached) in the control group, with a hazard ratio of 0.53 (99% CI 0.32-0-89; one-sided p=0-0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEA Es led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEA Es during study treatment occurred in six (3%) versus four (3%) patients. Interpretation The addition of isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population.
- Systemic amyloidosis journey from diagnosis to outcomes: a twelve-year real-world experience of a single center in a middle-income country(2022) SZOR, Roberta Shcolnik; FERNANDES, Fabio; LINO, Angelina Maria Martins; MENDONCA, Leonardo Oliveira; SEGURO, Fernanda Salles; FEITOSA, Valkercyo Araujo; CASTELLI, Jussara Bianchi; JORGE, Lecticia Barbosa; ALVES, Lucas Bassolli de Oliveira; NEVES, Precil Diego Miranda de Menezes; SOUZA, Evandro de Oliveira; CAVALCANTE, Livia Barreira; MALHEIROS, Denise; KALIL, Jorge; MARTINEZ, Gracia Aparecida; ROCHA, VandersonBackground: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients' medical records were retrospectively reviewed. Results: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, & GE; 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had & GE; 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG & GE; 2 were identified as independent risk factors for reduced survival. Conclusions: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.
- Guidelines on the diagnosis and management of multiple myeloma treatment: Associacao Brasileira de Hematologia e Hemoterapia e Terapia Celular Project guidelines: Associacao Medica Brasileira - 2022. Part I(2022) MAIOLINO, Angelo; CRUSOE, Edvan de Queiroz; MARTINEZ, Gracia Aparecida; BRAGA, Walter Moises Tobias; FARIAS, Danielle Leao Cordeiro de; BITTENCOURT, Rosane Isabel; PINTO NETO, Jorge Vaz; RIBEIRO, Glaciano Nogueira; BERNARDO, Wanderley Marques; TRISTAO, Luca; MAGALHAES, Roberto J. P.; HUNGRIA, Vania Tietsche de Moraes
- Acquired von willebrand syndrome secondary to monoclonal gammopathy of undetermined significance: long-term remission after treatment with bortezomib(2023) SALDANHA, Artur; VEIGA, Maria Eduarda; OKAZAKI, Erica; ROTHSCHILD, Cynthia; MARTINEZ, Gracia; ROCHA, Vanderson; ORSI, Fernanda A.; VILLACA, PaulaMonoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder that can precede the diagnosis of multiple myeloma. MGUS is characterized by the presence of a monoclonal paraprotein without evidence of multiple myeloma or other lymphoplasmacytic malignancies. Even though MGUS is an asymptomatic condition that does not require management strategies other than periodic follow-up to prevent complications, secondary nonmalignant diseases may arise, requiring control of the plasma cell clone. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that occurs in patients with no prior personal or family history of bleeding. It is associated with several other disorders, such as neoplasia, mainly hematological (including MGUS and other lymphoproliferative disorders), autoimmune, infectious and cardiac diseases. At diagnosis, patients usually present with cutaneous and mucosal bleeding, including gastrointestinal bleeding. Here, we report a case of a patient with MGUS who developed AVWS after one year of follow-up. The patient was refractory to glucocorticoids and cyclophosphamide and achieved remission only after monoclonal paraprotein was eradicated following treatment with bortezomib and dexamethasone. Our report sdemonstrates that, for refractory cases, eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS.
- Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation(2020) CRUSOE, Edvan De Queiroz; HIGASHI, Fabiana; MARTINEZ, Gracia; BITTENCOURT, Rosane; PINTO NETO, Jorge Vaz; SOUSA, Lais; SANTUCCI, Rodrigo; MAGALHÃES, Roberto José Pessoa; COLLI, Gilberto; NUNES, Renata Ferreira Marques; RIBEIRO, Glaciano; NICACIO, Jandir; ZANELLA, Karla Richter; KUTNER, Jose Mauro; MAGALHAES, Andre; LEAO, Danielle; HALLACK NETO, Abrahão Elias; BRAGA, Walter; SOUZA, Emanuella G; GUIMARAES, Antonio Julio A.M.; DURIGON, Giovanna Steffenello; LAKS, Dani; MAIOLINO, Angelo; HUNGRIA, Vania Tietsche de MoraesABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.
- Safety and Feasibility Analysis of a Prospective Trial on Stereotactic Body Radiotherapy for Solitary Bone Plasmacytoma(2021) MAURO, Geovanne Pedro; NEFFA, Pedro Pereira; VILLAR, Rosangela Correa; MARTINEZ, Gracia Aparecida; CARVALHO, Heloisa de AndradeBackground: There have been reports on the use of hypofractionated stereotactic body radiotherapy (SBRT) for bone plasmacytomas, but no prospective data are available. We present the initial analysis of an ongoing prospective protocol on SBRT addressing the feasibility and safety of this treatment for solitary bone plasmacytomas. Patients and Methods: A prospective cohort of SBRT for solitary bone plasmacytoma was developed. Patients could receive different doses depending on the index bone, from single fraction for skull base lesions, 24 Gy in 3 fractions for spine lesions, and 30 Gy in 5 fractions for other bones. Overall survival, bone events, local control, and progression to multiple myeloma (MM) were measured and compared to our retrospective cohort of patients treated with conformal standard-dose radiotherapy. Quality of life was assessed via the EORTC QLQ-C30 questionnaire, and toxicities were assessed by the CTCAE v5.0 criteria. After 1 year or the inclusion of 5-10 patients, a feasibility and safety analysis was programmed. Results: Between April 2018 and April 2019, 5 patients were included. All were male, with a median age of 53.1 years. The median follow-up was 21.8 months. No patient had local progression, bone event, or died. Two patients had progressions to MM. The mean survival free of progression to MM was 18.6 months, compared to 19 months in the retrospective cohort; median values were not reached. There were no grade 3 toxicities. Conclusion: SBRT for plasmacytoma is safe and feasible. More robust data are awaited.
- Long-term clinical outcomes in a cohort of patients with solitary plasmacytoma treated in the modern era(2019) SHARPLEY, F. A.; NEFFA, P.; PANITSAS, F.; KOTHARI, J.; SUBESINGHE, M.; CUTTER, D.; SZOR, R. Shcolnik; MARTINEZ, G. Aparedcida; ROCHA, V; RAMASAMY, K.Background The risk of recurrence of solitary plasmacytoma (SP)/progression to MM is well established, but patient, imaging and treatment factors influencing risk of progression require further evaluation. Methods This is a retrospective analysis of 66 SP patients (23 UK, 43 Brazil) diagnosed 1989-2016. Patient baseline characteristics were recorded. The incidence of progression to MM was calculated, including biochemical and imaging findings and the treatment modality received. Survival estimates were determined by Kaplan-Meier analyses. Results With a median follow-up of 53.6 months the 5 year overall survival (OS) was 90.7% (95%CI 79-96%). The median progression free survival (PFS) from diagnosis was 61 months. Cumulative incidence of progression to MM was 49.9% at 5 years (95% CI 35.6-62.6%) and was significantly higher with bone plasmacytoma (47.2%, 95%CI 31.9-61.1%), than an extramedullary location (8.3%, 95%CI 0.4-32.3%, Gray test p = 0.0095)). The majority of patients with solitary bony plasmacytoma (SBP) received radiotherapy (RT) (51/53, 96.2%) whereas most extramedullary cases were treated with surgical resection (7/13, 53.8%). A small proportion of SBP patients received additional upfront chemotherapy, with 5/6 in remission after a median follow-up (FU) of 10 years. The diagnostic yield of surveillance functional FU imaging without other indications of relapse/progression was low. The positive predictive value of functional FU imaging was high but with a low negative predictive value, especially in cases of suspected relapse/progression. Conclusion Our data suggests functional imaging should be used if clinical suspicion of relapse/progression, rather than a routine surveillance tool, and upfront adjuvant chemotherapy is worthy of prospective evaluation.