RESUMO
Asparaginase therapy is a vital agent in the treatment of acute lymphoblastic leukemia (ALL), with increasing evidence of its high importance in high-risk ALL populations. However, despite the clear clinical and biological benefits of asparaginase therapy, many patients experience toxicities. A well-known treatment-limiting toxicity is asparaginase-associated pancreatitis (AAP). If severe, it necessitates discontinuation of asparaginase therapy, which can lead to a higher risk of relapse in patients with ALL. New protocols for ALL therapy have increased overall total doses of asparaginase therapy in select high-risk populations and have incorporated longer half-life formulations of pegylated asparaginase. Treatment drug monitoring has also allowed assurance of adequate levels of asparagine depletion throughout treatment. It is currently unknown if these changes will increase rates of AAP. Interestingly, important pharmacogenomics data, such as single nucleotide polymorphisms, can identify patients at the highest risk for severe AAP. The incidence of AAP in recent trials, current pharmacogenomic data that could further our understanding of the disease, and the importance of cautiously re-exposing patients to further asparaginase treatment after an initial episode of AAP are discussed.
Assuntos
Antineoplásicos , Pancreatite , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Criança , Humanos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoAssuntos
Resistencia a Medicamentos Antineoplásicos , Imunoterapia Adotiva/métodos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Adolescente , Adulto , Idoso , Autoantígenos , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Overall survival of adolescents with relapsed T-cell lymphoblastic lymphoma (T-LL) remains poor with limited options for salvage therapy. The BCL-2 inhibitor venetoclax combined with hypomethylating agents like decitabine, has shown favorable responses in elderly patients with acute myeloid leukemia. OBSERVATION: We present the case of a 19-year-old adolescent with stage III relapsed and refractory T-LL who did not respond to 3 lines of salvage therapy. The patient was treated with venetoclax and decitabine and achieved a dramatic response. CONCLUSION: This case highlights the potential clinical activity of venetoclax and decitabine in relapsed T-LL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Adulto , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Decitabina/administração & dosagem , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico , Sulfonamidas/administração & dosagem , Adulto JovemRESUMO
Neurofibromatosis Type 1 (NF1) is a genetic disorder with an incidence of 1 in 2600 to 3000 individuals. It is a clinical diagnosis characterized by café-au-lait macules, neurofibromas, and axillary and/or groin freckling. Because of genetic mutations in the NF1 gene affecting the Ras/mitogen-activated protein kinase pathway, there is also risk of associated soft tissue sarcomas and hematologic malignancies. However, reports of classic Hodgkin lymphoma in patients with NF1 are sparse. We report an adolescent with NF1 who developed classic Hodgkin lymphoma. Although there is an unclear association between mutations in the NF1 gene and classic Hodgkin lymphoma, further studies are warranted.
Assuntos
Doença de Hodgkin/complicações , Neurofibromatose 1/complicações , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Manchas Café com Leite/complicações , Manchas Café com Leite/tratamento farmacológico , Manchas Café com Leite/genética , Manchas Café com Leite/patologia , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/genética , Doença de Hodgkin/patologia , Humanos , Mutação , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Neurofibromina 1/genéticaRESUMO
Myeloproliferative neoplasms (MPN) are rare disorders in young patients, and because of this, standardized treatment recommendations are not available. Pediatric patients are more frequently treated with hydroxyurea than interferon, yet there are no data suggesting this is the best practice. Current treatment guidelines for adults suggest using interferon as upfront therapy in young patients. We reviewed the cases of 13 young patients with polycythemia vera or essential thrombocythemia, who were treated with interferon. Extreme thrombocytosis was well controlled and the medication was tolerated by many. Our work shows the need for prospective studies evaluating interferon in our youngest patients with MPN.
Assuntos
Antivirais/uso terapêutico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Policitemia Vera/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Trombocitemia Essencial/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Policitemia Vera/patologia , Prognóstico , Proteínas Recombinantes/uso terapêutico , Trombocitemia Essencial/patologia , Adulto JovemRESUMO
BACKGROUND: Recurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report a first-in-human, phase I study of intraventricular infusions of ex vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies. METHODS: Twelve patients were enrolled, 9 received protocol therapy up to 3 infusions weekly, in escalating doses from 3 × 106 to 3 × 108 NK cells/m2/infusion, for up to 3 cycles. Cerebrospinal fluid (CSF) was obtained for cellular profile, persistence, and phenotypic analysis of NK cells. Radiomic characterization on pretreatment MRI scans was performed in 7 patients, to develop a non-invasive imaging-based signature. RESULTS: Primary objectives of NK cell harvest, expansion, release, and safety of 112 intraventricular infusions of NK cells were achieved in all 9 patients. There were no dose-limiting toxicities. All patients showed progressive disease (PD), except 1 patient showed stable disease for one month at end of study follow-up. Another patient had transient radiographic response of the intraventricular tumor after 5 infusions of NK cell before progressing to PD. At higher dose levels, NK cells increased in the CSF during treatment with repetitive infusions (mean 11.6-fold). Frequent infusions of NK cells resulted in CSF pleocytosis. Radiomic signatures were profiled in 7 patients, evaluating ability to predict upfront radiographic changes, although they did not attain statistical significance. CONCLUSIONS: This study demonstrated feasibility of production and safety of intraventricular infusions of autologous NK cells. These findings support further investigation of locoregional NK cell infusions in children with brain malignancies.
Assuntos
Neoplasias Encefálicas , Neoplasias Cerebelares , Ependimoma , Células Matadoras Naturais/transplante , Meduloblastoma , Adolescente , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/terapia , Neoplasias Cerebelares/líquido cefalorraquidiano , Neoplasias Cerebelares/terapia , Criança , Ependimoma/líquido cefalorraquidiano , Ependimoma/tratamento farmacológico , Feminino , Humanos , Infusões Intraventriculares , Células Matadoras Naturais/imunologia , Masculino , Meduloblastoma/líquido cefalorraquidiano , Meduloblastoma/terapia , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) have dismal outcomes. Preclinical studies have suggested that T-ALL cells are sensitive to BCL2 inhibition. The clinical activity of venetoclax, a selective BCL2 inhibitor, in T-ALL is unknown. PATIENT AND METHODS: We retrospectively reviewed the efficacy and safety of venetoclax combined with chemotherapy for patients with R/R T-ALL treated at our institution. RESULTS: Thirteen patients with R/R T-ALL with a median age of 46 years (range, 20-75 years) were treated with venetoclax plus chemotherapy. Five patients (38%) had early T-cell precursor ALL. The patients had received a median of 2 previous lines of therapy (range, 1-11). Venetoclax at a median dose of 200 mg/d for 21 days, generally with a concomitant azole antifungal, was combined with various agents, including hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), asparaginase, nelarabine, decitabine, or other intensive chemotherapy. Of the 10 patients evaluable for bone marrow response, 6 (60%) achieved a remission with bone marrow blasts < 5%, including 3 with complete hematologic recovery. The median overall survival and relapse-free survival were 7.7 and 4.0 months, respectively. No early death or clinically significant tumor lysis syndrome were reported. The median interval to neutrophil recovery and platelet recovery were 15 days and 44 days, respectively, with prolonged cytopenias observed with venetoclax 400 mg/d or when given for > 14 days per cycle. CONCLUSION: Combination therapy with venetoclax showed promising clinical efficacy in R/R T-ALL. Further studies are warranted to evaluate the clinical benefit of BCL2 inhibitors in T-ALL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Sulfonamidas/administração & dosagem , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
For several decades, few substantial therapeutic advances have been made for patients with acute myeloid leukaemia. However, since 2017 unprecedented growth has been seen in the number of drugs available for the treatment of acute myeloid leukaemia, with several new drugs receiving regulatory approval. In addition to advancing our therapeutic armamentarium, an increased understanding of the biology and genomic architecture of acute myeloid leukaemia has led to refined risk assessment of this disease, with consensus risk stratification guidelines now incorporating a growing number of recurrent molecular aberrations that aid in the selection of risk-adapted management strategies. Despite this promising recent progress, the outcomes of patients with acute myeloid leukaemia remain unsatisfactory, with more than half of patients ultimately dying from their disease. Enrolment of patients into clinical trials that evaluate novel drugs and rational combination therapies is imperative to continuing this progress and further improving the outcomes of patients with acute myeloid leukaemia.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Indução de Remissão , Aminoglicosídeos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação , Citarabina/administração & dosagem , Gemtuzumab , Genômica , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Seleção de Pacientes , Recidiva , Medição de Risco , Fatores de Risco , Estaurosporina/análogos & derivados , Estaurosporina/uso terapêuticoRESUMO
IMPORTANCE: The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. OBJECTIVE: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL. DESIGN, SETTING, AND PARTICIPANTS: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston. INTERVENTIONS: The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini-hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses). Inotuzumab was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles. MAIN OUTCOMES AND MEASURES: The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate. RESULTS: Fifty-nine patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated. Overall, 46 patients (78%) responded, 35 of them (59%) achieving complete response. The overall MRD negativity rate among responders was 82%. Twenty-six patients (44%) received ASCT. Grade 3 to 4 toxic effects included prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8). Veno-occlusive disease (VOD) occurred in 9 patients (15%). With a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively. The 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P = .03). CONCLUSIONS AND RELEVANCE: The combination of inotuzumab with low-intensity mini-HCVD chemotherapy shows encouraging results in R/R ALL. The risk of VOD should be considered carefully in patients with previous liver damage and among transplant candidates. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01371630.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Terapia de Salvação/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Inotuzumab Ozogamicina , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Análise de Sobrevida , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
PURPOSE: Nuclear medicine studies have previously been utilized to assess for blockage of cerebrospinal fluid (CSF) flow prior to intraventricular chemotherapy infusions. To assess CSF flow without nuclear medicine studies, we obtained cine phase-contrast MRI sequences that assess CSF flow from the fourth ventricle down to the sacrum. METHODS: In three clinical trials, 18 patients with recurrent malignant posterior fossa tumors underwent implantation of a ventricular access device (VAD) into the fourth ventricle, either with or without simultaneous tumor resection. Prior to infusing therapeutic agents into the VAD, cine MRI phase-contrast CSF flow sequences of the brain and total spine were performed. Velocity encoding (VENC) of 5 and 10 cm/s was used to confirm CSF flow from the fourth ventricular outlets to the cervical, thoracic, and lumbar spine. Qualitative CSF flow was characterized by neuroradiologists as present or absent. RESULTS: All 18 patients demonstrated CSF flow from the outlets of the fourth ventricle down to the sacrum with no evidence of obstruction. One of these patients, after disease progression, subsequently showed obstruction of CSF flow. No patient required a nuclear medicine study to assess CSF flow prior to initiation of infusions. Fourteen patients have received infusions to date, and none has had neurological toxicity. CONCLUSIONS: CSF flow including the fourth ventricle and the total spine can be assessed noninvasively with phase-contrast MRI sequences. Advantages over nuclear medicine studies include avoiding both an invasive procedure and radiation exposure.
Assuntos
Antineoplásicos/administração & dosagem , Líquido Cefalorraquidiano/diagnóstico por imagem , Quarto Ventrículo/diagnóstico por imagem , Neoplasias Infratentoriais/diagnóstico por imagem , Infusões Intraventriculares , Imageamento por Ressonância Magnética/métodos , Adolescente , Criança , Pré-Escolar , Meios de Contraste , Estudos de Avaliação como Assunto , Feminino , Quarto Ventrículo/efeitos dos fármacos , Humanos , Lactente , Neoplasias Infratentoriais/tratamento farmacológico , Masculino , Adulto JovemAssuntos
Toxinas Bacterianas/uso terapêutico , Exotoxinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Terapia de Salvação/métodos , Adolescente , Idoso , Antineoplásicos , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
In children with newly diagnosed acute myeloid leukaemia (AML), myeloid sarcomas (MS) of the central nervous system (CNS) are rare. Since MS involving the CNS are potentially curable, timely recognition is paramount. Establishing a diagnosis may be problematic as they can easily mimic primary CNS neoplasms. We report the case of a 5-year-old boy with AML with t(8;21)(q22;q22) rearrangement who presented with a massive intracranial MS and rapid clinical deterioration suggestive of a meningioma or a primitive neuroectodermal tumour. The peripheral smear showed blasts with Auer rods. Urgent chemotherapy was started for AML with presumptive CNS MS. The mass resolved with chemotherapy, and treatment was consolidated with radiotherapy. Although exceedingly rare, this case highlights the potential for MS to present similarly to a primary CNS tumour. MS should be part of the differential diagnosis as part of a CNS mass, particularly if the complete blood count is abnormal.
Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Leucemia Mieloide Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/fisiopatologia , Pré-Escolar , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Sarcoma Mieloide/tratamento farmacológico , Sarcoma Mieloide/fisiopatologia , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fmsRESUMO
Acute lymphoblastic leukemia (ALL) in the adolescent and young adult (AYA) population is a difficult clinical problem. The AYA population, generally regarded as patients aged 15 to 39 years, currently draws a good deal of attention, particularly in the area of therapy selection. The current trend is to treat this group of patients with leukemia regimens based on pediatric protocols, and results comparing pediatric approaches versus adult approaches to treatment are maturing. Results are pending from a large US trial in which pediatric-based treatment is given to AYA patients with ALL. In tandem with these new clinical trials, researchers have reported disease features in the AYA group that may explain some of the differences in response to treatment observed in the AYA population compared with the pediatric population. In addition, unique social factors in this age group add to the complexity of ALL therapy in the AYA population. AYA patients are developing independence and separating from their parents. They tend to be noncompliant. Young adults suffer from a lack of health care insurance and poor access to clinical trials, and have specific concerns regarding toxicities, in particular fertility. Cancer 2017;123:2398-403. © 2017 American Cancer Society.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Desenvolvimento do Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Ensaios Clínicos como Assunto , Preservação da Fertilidade , Acessibilidade aos Serviços de Saúde , Humanos , Inotuzumab Ozogamicina , Seguro Saúde , Cooperação do Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Rituximab/uso terapêutico , Transplante de Células-Tronco , Translocação Genética/genética , Transplante Homólogo , Trissomia/genética , Adulto JovemRESUMO
BACKGROUND: Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis. METHODS: The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords "hemophagocytosis" and/or "lymphohistiocytosis." Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded. RESULTS: The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P = .34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P = .002). CONCLUSIONS: The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2857-2866. © 2016 American Cancer Society.
Assuntos
Linfo-Histiocitose Hemofagocítica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen, and its comparison with hyper-fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper-CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome- (Ph) negative ALL received ABFM from October 2006 through March 2014. Their outcome was compared to 102 AYA patients (median age 27 years), treated with hyper-CVAD at our institution. The complete remission (CR) rate was 93% with ABFM and 98% with hyper-CVAD. The 5-year complete remission duration (CRD) were 53 and 55%, respectively (P = 0.98). The 5-year overall survival (OS) rates were 60 and 60%, respectively. The MRD status on Day 29 and Day 84 of therapy was predictive of long-term outcomes on both ABFM and hyper-CVAD. Severe regimen toxicities with ABFM included hepatotoxicity in 41%, pancreatitis in 11%, osteonecrosis in 9%, and thrombosis in 19%. Myelosuppression-associated complications were most significant with hyper-CVAD. In summary, ABFM and hyper-CVAD resulted in similar efficacy outcomes, but were associated with different toxicity profiles, asparaginase-related with ABFM and myelosuppression-related with hyper-CVAD. Am. J. Hematol. 91:819-823, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Asparaginase/efeitos dos fármacos , Criança , Ciclofosfamida , Dexametasona , Doxorrubicina , Feminino , Humanos , Masculino , Células Mieloides/efeitos dos fármacos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Vincristina , Adulto JovemRESUMO
Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a recently recognized high-risk T lymphoblastic leukemia/lymphoma (T-ALL/LBL) subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL/LBL are poorly characterized. In this study, we compared the outcomes of adults with ETP-ALL/LBL who received treatment on frontline regimens with those of patients with other T-ALL/LBL immunophenotypic subtypes. Patients with newly diagnosed T-ALL/LBL who received frontline chemotherapy between the years 2000 and 2014 at The University of Texas MD Anderson Cancer Center were identified and immunophenotypically categorized into early, thymic, and mature per the World Health Organization (WHO) classification using CD1a and surface CD3 status. Patients with ETP-ALL/LBL were identified on the basis of the following immunophenotypes: CD1a(-), CD8(-), CD5(-)(dim), and positivity for 1 or more stem cell or myeloid antigens. A total of 111 patients with T-ALL/LBL (68% T-ALL; 32% T-LBL) with adequate immunophenotype data were identified. The median age was 30 years (range, 13-79). There was no difference in the outcomes of patients based on the WHO subtypes. Nineteen patients (17%) had ETP-ALL/LBL. The complete remission rate /complete remission with incomplete platelet recovery rate in patients with ETP-ALL/LBL was significantly lower than that of non-ETP-ALL/LBL patients (73% vs 91%;P= .03). The median overall survival for patients with ETP-ALL/LBL was 20 months vs not reached for the non-ETP-ALL/LBL patients (P= .008). ETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this T-ALL/LBL subset.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Adulto , Idoso , Antígenos CD1/genética , Complexo CD3/genética , Diferenciação Celular , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Células Precursoras de Linfócitos T/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The long-term efficacy of a combination of chemotherapy and dasatinib in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is not well established. METHODS: Patients received dasatinib with 8 cycles of alternating hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine, and prednisone for 2 years, which was followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplantation (SCT) received it during their first CR. RESULTS: Seventy-two patients with a median age of 55 years (range, 21-80 years) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic CR after 1 cycle, and 64 (93%) achieved a major molecular response at a median of 4 weeks (range, 2-38 weeks). Sixty-five patients (94%) were negative for minimal residual disease assessed by flow cytometry at a median of 3 weeks (range, 2-37 weeks). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. With a median follow-up of 67 months (range, 33-97 months), 33 patients (46%) were alive, and 30 (43%) were in CR; 12 underwent allogeneic SCT. Thirty-nine patients died (3 at induction, 19 after relapse, 7 after SCT performed during first CR, and 10 during CR). The median disease-free survival and overall survival were 31 (range, 0.3-97 months) and 47 months (range, 0.2-97 months), respectively. Seven relapsed patients had BCR-ABL kinase domain mutations, including 4 with T315I. CONCLUSIONS: A combination of chemotherapy with dasatinib is effective in achieving long-term remission for patients with newly diagnosed Ph + ALL.
Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dasatinibe/administração & dosagem , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Dasatinibe/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Adulto JovemRESUMO
We hypothesize that chemotherapy can be safely administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. For the first time in humans, methotrexate was infused into the fourth ventricle in children with recurrent, malignant brain tumors. A catheter was surgically placed into the fourth ventricle and attached to a ventricular access device. Cerebrospinal fluid (CSF) flow was confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily methotrexate infusions (2 milligrams). Disease response was monitored with serial MRI scans and CSF cytologic analysis. Trough CSF methotrexate levels were sampled. Five patients (3 with medulloblastoma and 2 with ependymoma) received 18, 18, 12, 9, and 3 cycles, respectively. There were no serious adverse events or new neurological deficits attributed to methotrexate. Two additional enrolled patients were withdrawn prior to planned infusions due to rapid disease progression. Median serum methotrexate level 4 h after infusion was 0.04 µmol/L. Range was 0.02-0.13 µmol/L. Median trough CSF methotrexate level 24 h after infusion was 3.18 µmol/L (range 0.53-212.36 µmol/L). All three patients with medulloblastoma had partial response or stable disease until one patient had progressive disease after cycle 18. Both patients with ependymoma had progressive disease after 9 and 3 cycles, respectively. Low-dose methotrexate can be infused into the fourth ventricle without causing neurological toxicity. Some patients with recurrent medulloblastoma experience a beneficial anti-tumor effect both within the fourth ventricle and at distant sites.