RESUMO
Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated.
Assuntos
Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Antígenos CD34 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemAssuntos
Antineoplásicos/efeitos adversos , Arabinonucleosídeos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças da Medula Espinal/induzido quimicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/fisiopatologia , Resultado do TratamentoRESUMO
INTRODUCTION: Brentuximab vedotin (BV) is a potent anti-CD30 antibody drug conjugate (ADC) that has been approved in relapsed or refractory Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT) and anaplastic large-cell lymphoma (ALCL). Beyond these consolidated indications, BV has been tested in a number of different settings with promising results, leading for example to the recent approval as a consolidation after ASCT in high-risk HL patients. AREAS COVERED: Main emerging areas of clinical investigation of BV include the use as a single-agent or in combination with bendamustine in first-salvage therapy of HL (bridge to ASCT), in the frontline setting in combination with AVD chemotherapy in HL and with CHP in ALCL, in relapsed or refractory cutaneous T-cell lymphomas and finally in diffuse large B-cell lymphomas (DLBCL) expressing CD30. Moreover, many new ADCs are currently under clinical evaluation, as for example the anti-CD79A polatuzumab vedotin in DLBCL. Expert commentary: In few years BV changed the therapeutic scenario of relapsed or refractory HL and ALCL and is rapidly moving toward first-line approval in combination with standard chemotherapy if ongoing randomized trials will demonstrate improved results. Combination strategies with bendamustine in first-salvage HL and with R-CHP in first-line DLBCL appear very promising.
Assuntos
Antineoplásicos/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma/tratamento farmacológico , Antígenos de Neoplasias , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin , Ensaios Clínicos como Assunto , Quimioterapia de Consolidação , Resistencia a Medicamentos Antineoplásicos , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Humanos , Imunoconjugados/farmacologia , Antígeno Ki-1/antagonistas & inibidores , Linfoma/diagnóstico , Linfoma/metabolismo , Linfoma não Hodgkin/tratamento farmacológico , Recidiva , Terapia de Salvação , Tetraspaninas/antagonistas & inibidores , Transplante AutólogoRESUMO
Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.