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1.
Hematol Oncol ; 35(3): 281-287, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26928577

RESUMO

Plerixafor has been used to improve peripheral blood stem cell (PBSC) mobilization in multiple myeloma, non-Hodgkin lymphoma, and very recently in Hodgkin lymphoma (HL) patients. Because prior studies have suggested that mobilization with plerixafor affects the composition of mobilized cells, there are concerns that this may in turn adversely impact the immune reconstitution and longer term outcomes of transplanted patients. However, data on the engraftment characteristics and long-term post-transplant outcomes in patients transplanted with plerixafor-mobilized PBSCs are lacking. This retrospective study examined the post-transplant outcomes of 105 consecutive adult HL patients, and compared the post-transplant outcomes of 21 patients who received plerixafor in addition to G-CSF ± chemotherapy because of poor mobilization with those of 84 patients who mobilized well without plerixafor. Despite collecting significantly lower CD34+ cell doses (median of 3.41 vs. 6.05 × 106 /kg, p < 0.0001) than control patients and requiring more collection days, plerixafor-mobilized patients showed comparable early engraftment characteristics, except for slightly delayed neutrophil engraftment (median: 11 vs.10 days, p = 0.002) and lower median neutrophil counts (2.1 vs. 2.6 × 109 /L, p = 0.04) at one month after transplant. No significant differences were observed in longer term post-transplant outcomes, including cell counts at 3, 6, and 12 months, RBC and platelet transfusion support during the first 120 days, relapse incidence, overall and progression-free survival rates up to two years post transplant. The use of plerixafor not only enabled poorly mobilizing HL patients to collect enough PBSCs to proceed to ASCT, but also to have similar post-transplant outcomes compared to patients who mobilized well with conventional regimens. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/uso terapêutico , Doença de Hodgkin/terapia , Adulto , Idoso , Benzilaminas , Transfusão de Sangue , Terapia Combinada , Ciclamos , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Recidiva , Indução de Remissão , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
2.
J Vasc Interv Radiol ; 28(4): 594-601, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28169138

RESUMO

PURPOSE: To describe outcomes of patients with malignant biliary obstruction who undergo salvage percutaneous biliary drainage after occlusion of endoscopic biliary stents. MATERIALS AND METHODS: A single-center retrospective review was performed of 47 patients (25 men, 22 women) who underwent percutaneous biliary drainage for recurrent obstruction after endoscopic stent placement between 2005 and 2015. Primary malignancies were bile duct (n = 13), colorectal (n = 11), gallbladder (n = 7), pancreas (n = 5), hepatocellular (n = 4), and other (n = 7). Indication for salvage drain placement was infection (n = 19) and jaundice or need to decrease bilirubin (n = 28). Kaplan-Meier and Cox regression methods were used for survival analysis. Logistic and multivariate regressions were employed to identify factors associated with survival. RESULTS: Median survival after salvage biliary drain placement was 1.8 months (95% confidence interval [CI], 1.3-2.7). Elevated international normalized ratio (INR) ≥ 1.5 before drainage was associated with poorer survival after drainage (median survival 0.7 months vs 2.4 months, P < .01). Median survival was shorter in 28 patients (64%) with bilirubin ≤ 2 mg/dL (34.2 µmol/L) after drainage (1.2 months vs 5.4 months, P < .001). Left-sided drain placement, elevated bilirubin, and elevated INR correlated with decreased likelihood of achieving bilirubin ≤ 2 mg/dL (34.2 µmol/L) (odds ratio [OR] 0.13, 95% CI, 0.02-0.71, P = .02; OR 0.18, 95% CI, 0.05-0.69, P = .01; OR 0.10, 95% CI, 0.01-0.90, P = .04). CONCLUSIONS: Survival is limited for most patients who undergo salvage percutaneous biliary drainage. Elevated bilirubin and INR before drainage portend a poor prognosis.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Colestase/terapia , Neoplasias do Sistema Digestório/complicações , Drenagem/instrumentação , Terapia de Salvação , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Biomarcadores/sangue , California , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/mortalidade , Colestase/diagnóstico por imagem , Colestase/etiologia , Colestase/mortalidade , Neoplasias do Sistema Digestório/diagnóstico por imagem , Neoplasias do Sistema Digestório/mortalidade , Drenagem/efeitos adversos , Drenagem/métodos , Drenagem/mortalidade , Feminino , Humanos , Coeficiente Internacional Normatizado , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação/efeitos adversos , Terapia de Salvação/mortalidade , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
3.
Support Care Cancer ; 23(11): 3141-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25791390

RESUMO

PURPOSE: The purpose of this study is to assess the impact of palifermin on oral mucositis (OM) and its sequelae in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were conditioned with fractionated total body irradiation (FTBI) and etoposide. METHODS: This retrospective chart review study compared the effect of palifermin on the development of OM in patients who received this agent during an allo-HSCT (n = 99) to those who did not (n = 30). The primary end points were severity and duration of OM. Secondary end points included requirements for opioids, total parenteral nutrition (TPN), and intensive oral care; incidence of infection; length of hospital stay; and overall survival. RESULTS: There was no significant difference in the incidence of all grades of OM, but incidence of severe OM was decreased in palifermin-exposed patients (34 vs 80 %, p < 0.0001). In patients who developed OM (all grades), the median duration of OM was shorter in palifermin-exposed patients (13 vs 18 days, p = 0.0001); there was no difference in the median duration of severe OM. Patients who received palifermin used less opioids and required a shorter duration of intensive oral care. There was no difference in duration of TPN, incidence of infection, length of hospital stay, and overall survival. CONCLUSIONS: Our findings demonstrated a significant benefit with the use of palifermin for allo-HSCT recipients who were conditioned with FTBI and etoposide. Palifermin can potentially improve quality of life for this patient population and reduce complications and resources used during the transplant process. A randomized clinical trial is required to confirm these results.


Assuntos
Etoposídeo/efeitos adversos , Fator 7 de Crescimento de Fibroblastos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estomatite/prevenção & controle , Irradiação Corporal Total/efeitos adversos , Adolescente , Adulto , Etoposídeo/uso terapêutico , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral Total , Qualidade de Vida , Estudos Retrospectivos , Estomatite/etiologia , Adulto Jovem
4.
Endocr Pract ; 21(2): 128-35, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25297665

RESUMO

OBJECTIVE: Ultrasound-guided core needle biopsy (UG-CNB) is a procedure that is often performed either after repeated inadequate or nondiagnostic ultrasound-guided fine-needle aspiration (UG-FNA) or in combination with UG-FNA in the evaluation of thyroid nodules. The purpose of this study was to compare the efficacy and safety of UG-CNB and UG-FNA for evaluating thyroid nodules. METHODS: This was a retrospective study of 350 consecutive patients who had thyroid nodules biopsied by UG-CNB or UG-FNA from January 2007 until November 2011 at our institution. Biopsy results were compared to the surgical specimen pathology reports for the 105 patients who subsequently underwent hemi- or total thyroidectomy in order to determine whether UG-CNB has advantages over UG-FNA for diagnosing thyroid malignancy and neoplasia. RESULTS: Out of 461 thyroid nodules biopsied from 350 patients, 365 (79%) involved UG-CNB and 96 (21%) involved UG-FNA. The UG-FNA biopsy group had a significantly higher rate of inadequate sampling than the UG-CNB group (P<.0001; Fisher's exact test). Out of 365 UG-CNB samples, 6 (2%) were deemed inadequate for histologic diagnosis, whereas 26 (27%) of the 96 UG-FNA samples were considered inadequate for cellularity. Comparison of biopsy results with the surgical specimen pathology reports revealed that the diagnostic accuracy of UG-CNB and UG-FNA for detecting malignancy was similar, at 89 and 94%, respectively (not significant by Fisher's exact test). However, the UG-CNB group had a higher detection rate for benign follicular lesions compared to the UG-FNA group (65% versus 48% for UG-FNA; P = .002). Although UG-FNA detected neoplasia with high sensitivity (100%), the specificity was poor (30%). Neither biopsy group had any significant immediate or delayed procedure-related complications. CONCLUSION: Our study demonstrated that UG-CNB is safe and is less likely to result in a nondiagnostic biopsy. The accuracy of the UG-CNB technique is similar to that of UG-FNA for detecting thyroid malignancy.


Assuntos
Biópsia por Agulha Fina/métodos , Nódulo da Glândula Tireoide/patologia , Ultrassonografia de Intervenção , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Blood ; 117(1): 309-15, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-20876852

RESUMO

This phase 1/2 study assessed the augmentation of reduced-intensity conditioning (RIC) with total marrow and lymph node irradiation (TMLI), for peripheral blood stem cell transplantation, in patients with advanced hematologic disease. The regimen consisted of fludarabine 25 mg/m(2) per day for 5 days, melphalan 140 mg/m(2) for one day, and TMLI radiation at 150 cGy/fraction in 8 fractions over 4 days. Eligible patients were over 50 years old and/or had compromised organ function. Median age of the 33 evaluable patients was 55.2 years. Eighteen events of nonhematologic grade III or higher toxicities occurred in 9 patients. Day 30 and day 100 mortalities were 3% and 15%, respectively. Patients achieved myeloid and platelet engraftment at a median of 14 days after transplantation. Long-term toxicities occurred in 2 patients: hypokalemia and tremor, both grade III, on days 370 and 361 after transplantation. Fourteen patients died, 7 of relapse-related causes and 7 of non-relapse-related causes. With a median follow-up for living patients of 14.7 months, 1-year overall survival, event-free survival, and non-relapse-related mortality were 75%, 65%, and 19%, respectively. Addition of TMLI to RIC is feasible and safe and could be offered to patients with advanced hematologic malignancies who might not otherwise be candidates for RIC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/efeitos da radiação , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Linfonodos/efeitos da radiação , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Criança , Estudos de Viabilidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/patologia , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
6.
Biol Blood Marrow Transplant ; 18(3): 432-40, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21801703

RESUMO

Clofarabine is a novel purine nucleoside analog with immunosuppressive and antileukemia activity. We performed a phase I study of the combination of clofarabine plus melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with acute myelogenous leukemia. Patients over age 18 in complete remission or with active disease (up to 50% marrow blasts) who had a matched related or unrelated donor were eligible. The conditioning regimen consisted of escalating doses of clofarabine plus melphalan, followed by allogeneic stem cell transplantation. Sixteen patients (median age, 63 years) were treated at 3 dose levels; 4 of these patients had primary induction failure, and 3 were in first relapse. One patient at dose level 2 and 1 patient at dose level 3 died of multiorgan toxicity; no other dose-limiting toxicities were seen. All other patients at both doses of clofarabine studied demonstrated complete engraftment by day 30, with a median time to absolute neutrophil count recovery of 14 days, and 16 days for platelet recovery. With a median follow-up of 17 months, only 2 patients relapsed, and 4 patients died. Clofarabine plus melphalan at dose level 2 is a well-tolerated conditioning regimen with activity in patients with advanced acute myelogenous leukemia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Nucleotídeos de Adenina/administração & dosagem , Nucleotídeos de Adenina/efeitos adversos , Adulto , Idoso , Arabinonucleosídeos/administração & dosagem , Arabinonucleosídeos/efeitos adversos , Clofarabina , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/cirurgia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo
7.
Eur Radiol ; 22(10): 2273-81, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22618523

RESUMO

OBJECTIVE: To investigate the risk factors for, and the incidence of, structural abnormalities on brain imaging in allogeneic haematopoietic stem cell transplant (HSCT) patients, and correlate these findings with survival. METHODS: We retrospectively reviewed all brain computed tomography (CT) and/or magnetic resonance imaging (MRI) studies obtained during the first post-HSCT year from 2004 thru 2007 in allogeneic HSCT recipients. RESULTS: A total of 128 patients had brain imaging in the first post-HSCT year. Forty one of these 128 patients (32 %) had structural abnormalities on brain imaging: cerebrovascular complications (n = 10), central nervous system (CNS) infection (n = 9), subdural fluid collection (n = 6), CNS recurrence of haematological malignancy (n = 11), and drug toxicity abnormalities (n = 5). The only significant risk factor for structural imaging abnormality was younger patient age (P = 0.01). MRI was significantly more likely than CT to provide specific imaging diagnosis of cerebral lesions (P = 0.001). HSCT patients with cerebrovascular complications have poor survival (P < 0.05). However, overall survival was not significantly worse for the 41 patients with the structural imaging abnormalities as compared to the 87 patients who had brain imaging but no structural abnormalities. CONCLUSIONS: There was no survival difference in patients whose brain imaging was normal or abnormal. However, there was poor outcome in patients with cerebrovascular complications after HSCT. KEY POINTS : • Brain imaging frequently demonstrates neurological complications following haematopoietic stem cell transplantation. • Younger HSCT patients are more likely to exhibit abnormal brain imaging findings. • HSCT recipients with cerebrovascular complications have the worst survival. • However brain imaging results are weak indicators of overall survival after HSCT.


Assuntos
Encefalopatias/diagnóstico , Encefalopatias/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imageamento por Ressonância Magnética , Neuroimagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Encefalopatias/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
8.
Biol Blood Marrow Transplant ; 17(11): 1662-72, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21596150

RESUMO

The important role of activating killer immunoglobulin-like receptors (KIRs) in protecting against cytomegalovirus (CMV) reactivation has been described previously in patients undergoing hematopoietic cell transplantation (HCT). More specifically, the presence of multiple activating KIRs and the presence of at least KIR2DS2 and KIR2DS4 in the donor genotype identified a group of HCT patients at low risk for CMV reactivation. However, CMV infection still occurs in patients with the KIR protective genotype, and the question has been raised as to whether this is related to the lack of KIR expression. In this report, expression of the KIR2DS2 and KIR2DS4 genes, as measured by mRNA-based quantitative polymerase chain reaction in both the donor cells and the HCT recipient cells, was studied relative to CMV reactivation. In the control samples from healthy donors, the median range for KIR2DS2 and KIR2DS4 expression was low, with 35% of donors considered null-expressers. Interestingly, KIR2DS2 and KIR2DS4 expression was elevated after HCT compared with donor expression before HCT, and was significantly elevated in CMV viremic compared with CMV nonviremic HCT recipients. The CMV seropositivity of donors was not associated with activating KIR expression, and donor null expression in those with the KIR2DS2 or KIR2DS4 genotype was not predictive for CMV reactivation in the recipient. After controlling for other transplant factors, including donor type (sibling or unrelated), transplant source (bone marrow or peripheral blood stem cells), and acute GVHD grade, regression analysis of elevated KIR gene expression found an association for both KIR2DS2 and KIR2DS4, with a 7-fold increase in risk for CMV reactivation. We speculate that the elevated activating KIR expression in CMV-viremic HCT recipients is either coincidental with factors that activate CMV or is initiated by CMV or cellular processes responsive to such CMV infection reactivation.


Assuntos
Infecções por Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores KIR/biossíntese , Adulto , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/metabolismo , Feminino , Humanos , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores KIR/genética , Transplante Homólogo/efeitos adversos , Ativação Viral
9.
Transplant Cell Ther ; 27(1): 72.e1-72.e7, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007495

RESUMO

Forty-seven patients with metastatic disease at diagnosis or recurrent Ewing sarcoma (EWS) received high-dose chemotherapy (HDC) followed by tandem (n = 20, from February 13, 1997, to October 24, 2002) or single (n = 27, from October 1, 2004, to September 5, 2018) autologous hematopoietic stem cell transplantation (ASCT). To our knowledge, this is the largest single-institution study with sustained long-term follow-up exceeding 10 years. All patients who underwent single ASCT received a novel conditioning regimen with busulfan, melphalan, and topotecan. The overall survival (OS) and disease-free survival (DFS) were 46% and 37% at 10 years and 42% and 37% at 15 years, respectively. Disease status at transplant and the time to disease relapse prior to ASCT were identified as important prognostic factors in OS, DFS, and risk of relapse. At 10 years, patients who underwent transplantation in first complete response (1CR) had an excellent outcome (OS 78%), patients in 1CR/second complete response (2CR)/first partial response (1PR) had an OS of 66%, and patients at third or more complete response, second or more partial response, or advanced disease had an OS of 26%. Ten-year OS for patients without a history of relapse, with late relapse (≥2 years from diagnosis), or with early relapse (<2 years from diagnosis) was 75%, 50%, and 18%, respectively. Selected patients in 1CR, 2CR, 1PR, and with late relapse had excellent, sustained 10- and 15-year OS and DFS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sarcoma de Ewing , Criança , Seguimentos , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Transplante Autólogo , Adulto Jovem
11.
PLoS One ; 15(3): e0229955, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32150594

RESUMO

The evolutionary changes in immune profiles of triple negative breast cancer (TNBC) are not well understood, although it is known that immune checkpoint inhibitors have diminished activity in heavily pre-treated TNBC patients. This study was designed to characterize immune profile changes of longitudinal tumor specimens by studying immune subsets of tumor infiltrating lymphocytes (TILs) in paired primary and metastatic TNBC in a cohort of "poor outcome" (relapsed within 5 years) patients. Immune profiles of TNBCs in a cohort of "good outcome" (no relapse within 5 years) patients were also analyzed. Immune subsets were characterized for CD4, CD8, FOXP3, CD20, CD33, and PD1 using immuno-fluorescence staining in stroma, tumor, and combined stroma and tumor tissue. TIL subsets in "good outcome" versus "poor outcome" patients were also analyzed. Compared with primary, metastatic TNBCs had significantly lower TILs by hematoxylin and eosin (H&E) staining. Stromal TILs (sTILs), but not tumoral TILs (tTILs) had significantly reduced cytotoxic CD8+ T cells (CTLs), PD1+ CTLs, and total PD1+ TILs in metastatic compared with matched primary TNBCs. Higher PD1+ CTLs, PD1+CD4+ helper T cells (PD1+TCONV) and all PD1+ T cells in sTILs, tTILs and total stromal and tumor TILS (s+tTIL) were all associated with better prognosis. In summary, TIL subsets decrease significantly in metastatic TNBCs compared with matched primary. Higher PD1+ TILs are associated with better prognosis in early stage TNBCs. This finding supports the application of immune checkpoint inhibitors early in the treatment of TNBCs.


Assuntos
Linfócitos do Interstício Tumoral/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos CD/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Feminino , Imunofluorescência , Humanos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/imunologia
12.
Biol Blood Marrow Transplant ; 15(3): 315-25, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19203722

RESUMO

It has been shown that activating killer Ig-like receptor (aKIR) genes are important for control of cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation (HCT). To date, using the broad classification of KIR haplotypes A and B, the precise role of individual KIR genes in the control of infection cannot be discerned. To address this, a consecutive case series of 211 non-T cell-depleted HCT patients all at risk for CMV were monitored biweekly for CMV DNA in plasma by quantitative polymerase chain reaction (Q-PCR) and at intervals for CMV-specific T cell immunity. Comparing patients with CMV reactivation (n = 152) to those with no reactivation (n = 59), the presence of specific aKIR haplotypes in the donor, but not in the recipient, were associated with protection from CMV reactivation and control of peak plasma CMV DNA (P < .001). A donor aKIR profile, predictive for low risk of CMV reactivation, contained either aKIR2DS2 and aKIR2DS4 or had >/=5 aKIR genes. Neither donor nor recipient inhibitory KIR (iKIR) played a role in a protective effect. CD4(+)- and CD8(+)-specific CMV immunity did not explain reduced CMV infection. The initial control of CMV infection after HCT is managed by aKIR functions, and donor aKIR haplotypes deserve further evaluation in donor selection for optimized HCT outcome.


Assuntos
Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Transplante de Células-Tronco Hematopoéticas , Receptores KIR/genética , Receptores KIR/imunologia , Adulto , DNA Viral/imunologia , Feminino , Genótipo , Humanos , Imunidade/genética , Imunidade/imunologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doadores de Tecidos , Ativação Viral
13.
Biol Blood Marrow Transplant ; 15(7): 872-80, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19539220

RESUMO

To study the role of the programmed death-1 molecule (PD-1) in cytomegalovirus (CMV) infection and disease after allogeneic hematopoietic cell transplantation (HCT), 206 subjects were followed prospectively for immune response to CMV and assigned to 3 groups based on CMV outcome. The subjects were analyzed retrospectively for PD-1 expression in cryopreserved CD4+ and CD8+T cells collected at days 40, 90, 120, 150, 180, and 360 posttransplantation. HCT recipients with CMV disease (n=14) were compared with recipients with prolonged CMV infection, but no CMV disease (median duration of infection, 3 months; n=14) and with controls with no CMV infection who received similar transplants (n=22). The CMV disease group had a significantly higher mean fluorescein intensity of PD-1 in CD4+ (P < .05) and CD8+ (P < .05) lymphocytes at all time points studied. PD-1 expression also was significantly elevated in those with severe acute graft-versus-host disease (aGVHD), including the no-viremia group. The data suggest that PD-1 is induced by aGVHD even in the absence of CMV infection. This enhanced PD-1 expression during severe aGVHD and with CMV reactivation could explain the known role of aGVHD as a risk factor for CMV disease.


Assuntos
Antígenos CD/biossíntese , Proteínas Reguladoras de Apoptose/biossíntese , Infecções por Citomegalovirus/metabolismo , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Citomegalovirus , Feminino , Doença Enxerto-Hospedeiro/virologia , Humanos , Masculino , Receptor de Morte Celular Programada 1 , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Transplante Homólogo
14.
PLoS One ; 14(11): e0224726, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693690

RESUMO

The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34-0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41-0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33-23.1 and HR 8.0, 95% CI 1.53-41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01-1.16 and HR 1.05, 95% CI 1.00-1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Regulação Neoplásica da Expressão Gênica/imunologia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/imunologia , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Análise Mutacional de DNA , Intervalo Livre de Doença , Epitélio/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , PTEN Fosfo-Hidrolase/genética , Prognóstico , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética
15.
J Clin Oncol ; 21(4): 615-23, 2003 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-12586797

RESUMO

PURPOSE: To determine the disease-free survival (DFS) and toxicity of administering interleukin-2 (IL-2) immunotherapy early after autologous stem-cell transplantation (ASCT) to simulate a graft versus leukemia effect observed in allogeneic transplantation. PATIENTS AND METHODS: Fifty-six patients with acute myeloid leukemia in first remission received a single consolidation of high-dose cytarabine-idarubicin at a median of 1.1 month postremission with the intent to proceed to ASCT and IL-2 9 x 10(6) U/m(2)/24 h for 4 days, followed by 10 days of IL-2 1.6 x 10(6) U/m(2)/24 h on hematologic recovery. RESULTS: Eighty-four percent of patients received the intended ASCT, and 68% of patients received IL-2 treatment. With a median follow-up of 39.4 months (range, 1.2 to 76.3 months), the 2-year cumulative probability of DFS for all 56 patients is 68% (95% confidence interval [CI], 55% to 80%) and 74% (95% CI, 57% to 85%) for the 39 patients undergoing IL-2 treatment after ASCT. The 2-year cumulative probability of DFS for favorable, intermediate, and unfavorable cytogenetics is 88% (95% CI, 59% to 97%), 48% (95% CI, 26% to 67%), and 70% (95% CI, 23% to 93%), respectively. Toxicities from IL-2 were mainly thrombocytopenia, leukopenia, fever, and fluid retention. Two septic deaths occurred during neutropenia, which includes one during consolidation and one during transplant, for an overall 4% mortality rate. CONCLUSION: These results suggest that a moderate dose of IL-2 after high-dose cytarabine-idarubicin-mobilized ASCT is associated with a low regimen-related toxicity and may improve DFS. A phase III study of IL-2 is now warranted.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Interleucina-2/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Transplante de Células-Tronco , Adulto , Antineoplásicos/efeitos adversos , Intervalos de Confiança , Citarabina/administração & dosagem , Feminino , Humanos , Idarubicina/administração & dosagem , Interleucina-2/efeitos adversos , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade
16.
Biol Blood Marrow Transplant ; 13(2): 197-205, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17241925

RESUMO

In hematopoietic cell transplantation (HCT), natural killer cell alloreactivity conferred by inhibitory ligands of killer immunoglobulin-like receptors (iKIRLs) may result in beneficial or detrimental outcomes. More data may contribute to resolution of this complex issue. We analyzed 378 primary allogeneic transplants with T-replete grafts for acute lymphoblastic leukemia (n = 101), acute myeloid leukemia and myelodysplastic syndrome (n = 149), and chronic myeloid leukemia (n = 128). The cohort was divided into 3 groups: in group 1, HLA class I matched at the antigen level (n = 260); in group 2, HLA class I mismatched at the antigen level (n = 57); and in group 3, HLA class I and iKIRLs mismatched (n = 61). One-year overall survival (OS) across groups 1 (59%), 2 (49%), and 3 (30%) was significantly different (P = .002). In contrast to group 2, group 3 had statistically lower OS (P = .05) and event-free survival (P = .01). Relapse and relapse-free mortality appeared to contribute to the low OS in group 3. The detrimental effect of natural killer alloreactivity was also evident when HLA-matched transplants were analyzed for patients lacking iKIRLs. One-year OS in patients lacking the HLA-Cw group 1 or 2 iKIRL was significantly lower than that in patients having the iKIRLs (55% vs 67%, n = 246, P = .01). Our observations indicate that, in T-replete unrelated HCT, iKIRL mismatches and the absence of iKIRLs confer higher risk to patients after HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células Matadoras Naturais/imunologia , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Receptores Imunológicos/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Pessoa de Meia-Idade , Receptores KIR , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
17.
Transfusion ; 47(12): 2207-16, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17714420

RESUMO

BACKGROUND: The successful mobilization and collection of hematopoietic stem cells are dependent on a number of clinical factors such as previous chemotherapy and disease stage. The aim of this retrospective study was to determine whether the effectiveness of mobilization and collection is an independent prognostic factor for autologous stem cell transplantation outcome. STUDY DESIGN AND METHODS: A total of 358 patients who received transplants from January 2003 to December 2004 (201 male and 157 female patients, ages from 2.7 to 77.3 years with median of 53 years of age) underwent autologous hematopoietic stem cell collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. This retrospective study included patients with diagnoses of acute myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, and solid tumors. All patients underwent stem cell collection until a target or a minimum CD34+ cell dose was reached. Correlations were performed between stem cell mobilization and/or collection efficacy and transplantation outcomes. RESULTS: In general, both larger reinfused CD34+ cell dose and shorter number of days for the stem cell count to reach the minimum of 2 x 10(6) per kg CD34+ cells do not foster quicker engraftment. Reinfused CD34+ cell dose of less than 12 x 10(6) and number of days stem cell collection to reach this minimum CD34+ cell dose did not independently affect the overall survival (OS) or disease-free survival (DFS). CONCLUSION: The effectiveness of hematopoietic stem cell mobilization and collection as defined as number of days to reach a CD34+ cell dose of 2 x 10(6) per kg should not be used independently to forecast posttransplantation prognosis, engraftment, DFS, and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Idoso , Antígenos CD34/análise , Criança , Pré-Escolar , Terapia Combinada , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Doença de Hodgkin/metabolismo , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
18.
Biol Blood Marrow Transplant ; 12(6): 641-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16737937

RESUMO

The purpose of this study was to evaluate whether follicular histology in large cell lymphoma influences treatment outcomes after autologous stem cell transplantation (ASCT). It remains an area of controversy whether the natural history of follicular large cell lymphoma (FLCL) is akin to diffuse large cell lymphoma (DLCL) with curative potential or is more similar to indolent follicular lymphomas with a pattern of late relapses after intensive chemotherapy. Although ASCT is a potentially curative treatment for patients with recurrent DLCL, the effectiveness of this approach in patients with FLCL is unclear. We undertook a retrospective analysis of 332 patients with large cell lymphoma who underwent ASCT at the City of Hope Comprehensive Cancer Center. With a median follow-up of 31 months, the projected 10-year overall survival and disease-free survival were similar between patients with FLCL and DLCL. Analysis of prognostic factors demonstrated that although age, chemotherapy refractoriness, and disease status at the time of ASCT were predictive of overall survival/disease-free survival, follicularity did not influence the outcome. Furthermore, the similar plateau in the survival curve for the DLCL and FLCL patients suggests that the behavior of FLCL is similar to that of DLCL and that FLCL is potentially curable with ASCT.


Assuntos
Linfoma Folicular/patologia , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Transplante de Células-Tronco , Adulto , Medula Óssea/patologia , Intervalo Livre de Doença , Seguimentos , Humanos , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
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