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The use of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has resulted in reductions in GVHD and improved outcomes in allogeneic hematopoietic cell transplantation (HCT) using HLA-mismatched related donors. We report the 3-year outcomes of the first multicenter prospective clinical trial using PTCy in the setting of mismatched unrelated donor (MMUD) bone marrow HCT. The study enrolled 80 patients, treated with either myeloablative conditioning (MAC; n = 40) or reduced-intensity conditioning (RIC; n = 40), with the primary endpoint of 1-year overall survival (OS). The median follow-up for this study was 34 months (range, 12 to 46 months) in the RIC group and 36 months (range, 18 to 49 months) in the MAC group. Three-year OS and nonrelapse mortality were 70% and 15%, respectively, in the RIC group and 62% and 10% in the MAC group. No GVHD was reported after 1 year. The incidence of relapse was 29% in the RIC group and 51% in the MAC group. OS did not differ based on HLA match grade (63% in the 7/8 strata and 71% in the 4 to 6/8 strata). These encouraging outcomes, which were sustained for 3 years post-HCT, support the continued exploration of MMUD HCT using a PTCy platform. Important future areas to address include relapse reduction and furthering our understanding of optimal donor selection based on HLA and non-HLA factors.
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Medula Óssea , Doença Enxerto-Hospedeiro , Humanos , Seguimentos , Estudos Prospectivos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Doadores não Relacionados , RecidivaRESUMO
Mantle cell lymphoma is a rare subtype of non-Hodgkin's lymphoma with poor prognosis and continue to be challenging to treat. The choice of first line induction regimen remains a topic of debate due paucity of clinical trials. We retrospectively evaluated 66 patients diagnosed with mantle cell lymphoma who achieved first complete response after induction chemotherapy followed by autologous stem cell transplant. Treatment groups were divided into low-intensity versus high-intensity regimens. Our data showed the intensity of induction regimen does not impact posttransplant outcomes of mantle cell lymphoma who underwent autologous stem cell transplant in first complete response.
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Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto , Adulto , Humanos , Linfoma de Célula do Manto/terapia , Transplante Autólogo , Quimioterapia de Indução , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Indução de Remissão , Transplante de Células-TroncoRESUMO
Purpose: Women with locally advanced/high-risk triple-negative breast cancer treated with the current standard chemotherapy continue to have a poor prognosis. High-dose chemotherapy with autologous stem cell transplant as treatment for locally advanced/high-risk breast cancer remains controversial due to a lack of survival benefit seen in previous phase III trials. However, these trials evaluated a heterogeneous group of patients with different receptor subtypes. A marginal benefit was observed in certain subgroups. We report long-term outcomes of women with stage IIB or III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant at our institution between 1995 and 2001. Methods: This is a retrospective analysis of stage IIB or stage III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant. We excluded women with hormone-positive, HER2/neu-positive/unknown, and/or metastatic disease prior to transplant as per updated AJCC 7th edition guidelines. Patients underwent surgery and either neoadjuvant or adjuvant anthracycline and taxane-based chemotherapy and then proceeded to high-dose chemotherapy and autologous stem cell transplant using carmustine 600 mg/sqm, cyclophosphamide 5.6gm/sqm, and cisplatin 165 mg/sqm (STAMP 1 regimen) for consolidation. This was followed by locoregional breast and lymph node radiation per standard of care. Results: Twenty-nine women (2 stage IIB and 27 stage III) were evaluated. The median age at diagnosis was 43 years (IQR: 40, 51). Eleven patients had 4-9 regional lymph nodes (LN) involved and 16 had 10+ involved LNs. Four patients had T4 or inflammatory breast cancer and two had ipsilateral supraclavicular LNs involved. The median follow-up time is 16 years (95% CI: 12, 19, range <1-19 y) posttransplant. The median overall survival was 15 years (95% CI: 3, 19); the median DFS was 14 years (95% CI: 1, 19). Conclusions: This study of locally advanced/high-risk triple-negative breast cancer treated with adjuvant high-dose chemotherapy and autologous stem cell transplant reveals high overall survival rate. With the current improvement in treatment-related mortality, re-evaluating this approach in this subset of high-risk breast cancer in prospective randomized studies may be worthwhile.
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Utilization of novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CI) has increased in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL). We conducted a retrospective study of 209 patients who had ASCT for r/r cHL at our institution and compared outcomes of those who had ASCT from 2010-2018 (cohort 2, n = 110) with those who had ASCT between 2000 and 2009 (cohort 1, n = 99). The median OS was 7.6 years for cohort 1 [HR 2.08; 95% CI 1.14-3.80; p = 0.017] and not reached for cohort 2; with 4-year improved OS difference of 15% (80% vs 65%) in cohort 2 vs cohort 1. The median PFS of cohort 1 was 30 months vs 39 months for cohort 2[HR 1.24; 95% CI 0.82-1.88; p = 0.3]. This study highlights improved OS of r/r cHL patients who have received ASCT in the novel agent era due to the exposure to agents such as BV and CIs.
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Doença de Hodgkin , Imunoconjugados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Transplante AutólogoRESUMO
Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.
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Acetamidas/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento , Adulto Jovem , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
PURPOSE: Hematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT. PATIENTS AND METHODS: We performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy. RESULTS: Notably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS. CONCLUSION: Our prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.
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Ciclofosfamida/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Grupos Minoritários , Estudos Prospectivos , Sistema de Registros , Adulto JovemRESUMO
The use of G-CSF post allogeneic transplant has become a common practice to accelerate neutrophil engraftment. There is some controversy in its use. To further evaluate the effectiveness, we compared outcomes in patients who underwent PBSCT, either with or without the planned use of G-CSF post SCT. Among consecutive 162 patients from October 2012 to October 2014, 65 patients received G-CSF post-PBSCT, and 97 did not. More patients in G-CSF group received MAC (78% vs. 55%). Patients who received G-CSF had earlier neutrophil engraftment (median days 11 vs. 14) and shorter post-transplant hospital stay (median days 16 vs. 20, p = 0.001). G-CSF use was associated with a higher rate of extensive chronic GVHD (44.3% vs.61.5%, p = 0.027). G-CSF cost the equivalent of 0.25 hospital days but shortened the initial transplant admission by 4 days. Early cost-benefit may be later offset by the economic burden of chronic GVHD and associated complications.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Fator Estimulador de Colônias de Granulócitos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospitais , Humanos , Incidência , Tempo de Internação , Neutrófilos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante HomólogoRESUMO
Maintenance therapy after first autologous transplant (autoSCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). However, efficacy of maintenance therapy after second autoSCT is unknown. We retrospectively evaluated outcomes of 111 adult MM patients who underwent second autoSCT between January 2000 and December 2018. Lenalidomide up to 15 mg daily or subcutaneous bortezomib 1.3 mg/m2 every 2 weeks was considered maintenance therapy. Outcomes were compared among three groups: no-maintenance (n = 73), lenalidomide (n = 23), and bortezomib maintenance (n = 15). At a median follow-up of 58 months from second autoSCT for survival, 3-year PFS and OS for no-maintenance, lenalidomide, and bortezomib maintenance were 11.2%, 29.9%, and 0%, respectively; and 58.5%, 83.3%, and 67.5% respectively. Lenalidomide maintenance was associated with improved PFS (HR 0.46, p = 0.009) and OS (HR 0.25, p = 0.009) compared to no-maintenance. Lenalidomide maintenance therapy after second autoSCT appears to prolong PFS and OS.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Intervalo Livre de Doença , Humanos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante AutólogoRESUMO
Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients. We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n = 47) or reduced-intensity conditioning (RIC) regimens (n = 23). Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P = .03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P = .48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P = .96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P = .98), and relapse-free survival (RFS; 34.8% versus 34.7%, P = .75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P = .05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P = .04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Transplante de Células-Tronco , Condicionamento Pré-TransplanteRESUMO
Impact of Plerixafor (P) mobilized stem cells on immune reconstitution, such as absolute lymphocyte count at day 30 (ALC30), and on long-term outcomes of Multiple Myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) has not been well established. We evaluated total of 469 patients mobilized with G-CSF (G) alone, and 141 patients mobilized with G-CSF plus plerixafor (G+ P). Patients only received plerixafor if they had peripheral blood CD34+ blood count <20/µL on first planned day of collection. Primary endpoint, ALC30, was 1.3 K/µL (range, 0.1-4.5) and 1.2 K/µL (range, 0.1-5.1) for G and G + P, respectively (P =. 61). The median PFS was 2.5 years (95% CI, 2.1-3.2) and 2.8 years (95% CI, 2.0-3.3) for G and G + P, respectively (HR: 1.13; 95% CI, 0.84-1.50; P = .42). The median OS was 6.1 years (95% CI, 4.6-NR) for G group compared to 3.7 years (95% CI, 3.2-NR) for the G + P group (HR: 1.64; 95% CI, 1.12-2.40; P = .01). The median follow-up time for OS was 2.53 years (95% CI, 2.13-2.99) and 1.59 years (95% CI, 1.17-2.02) for G and G+ P group, respectively. In this large retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery or PFS. There was an overall survival difference in patients who were poor mobilizers and could not be mobilized with G-CSF alone.
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Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/administração & dosagem , Mieloma Múltiplo/terapia , Recuperação de Função Fisiológica , Adulto , Idoso , Autoenxertos , Benzilaminas , Ciclamos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a "non-liver GVHD" group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the "non-liver GVHD" group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.
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Biópsia/métodos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Falência Hepática/etiologia , Adulto , Aloenxertos , Biópsia/efeitos adversos , Intervalo Livre de Doença , Estudos de Viabilidade , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Hemorragia/etiologia , Humanos , Hiperbilirrubinemia/etiologia , Imunossupressores/uso terapêutico , Incidência , Sobrecarga de Ferro/complicações , Fígado/patologia , Falência Hepática/sangue , Falência Hepática/mortalidade , Falência Hepática/patologia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Modelos de Riscos Proporcionais , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Resultado do TratamentoRESUMO
Information on the use of hypomethylating agents (HMAs) as a pre-transplant cytoreductive therapy in MDS is limited. We retrospectively evaluated outcomes of 172 adult MDS patients, who underwent allogeneic hematopoietic stem cell transplantation between January 2000 and December 2016. Patients were divided into three groups: group 1 - pre-transplant blasts <5% with HMA (n = 42), group 2 - pre-transplant blasts ≥5% with HMA (n = 38), group 3 - no HMA (n = 92). With a median follow up of 4.08 years, 1-year survival and relapse rates for groups 1, 2, and 3 were 75%, 40.2%, and 60.71%, respectively; and 17.6%, 26.6%, and 9.8%, respectively. Multivariate analysis revealed adverse relapse (HR 3.54; p = .03) in group 2 compared to groups 1 and 3, while no difference in overall survival was noticed. Our study shows no survival association with pre-transplant HMA; although, higher relapse rate was observed in the non-responding patients indicating possible chemotherapy resistant disease.
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Metilação de DNA , Decitabina/uso terapêutico , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Síndromes Mielodisplásicas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Clostridioides difficile , Enterocolite Pseudomembranosa , Gastroenteropatias , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Aloenxertos , Intervalo Livre de Doença , Enterocolite Pseudomembranosa/etiologia , Enterocolite Pseudomembranosa/mortalidade , Enterocolite Pseudomembranosa/prevenção & controle , Feminino , Gastroenteropatias/etiologia , Gastroenteropatias/microbiologia , Gastroenteropatias/mortalidade , Gastroenteropatias/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/microbiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Família , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Doadores Vivos , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is potentially curative for patients with high-risk leukemia, but disease recurrence remains the leading cause of treatment failure. Our objective was to determine the impact of minimal residual disease (MRD) by any technique in adult patients with acute myeloid leukemia (AML) in morphologic first and second complete remission undergoing allo-SCT. Fifty nine patients were eligible for the study of 160 patients transplanted over ten years. For the MRD assessment we used multiparametric flow cytometry, cytogenetics and fluorescent in situ hybridization; 19 patients (32.2%) were identified as MRD positive. Patients with MRD had a consistently worse outcome over those without MRD, with 3-years leukemia-free survival (LFS) of 15.8% vs. 62.4% and overall survival (OS) of 17.5% vs. 62.3%. Relapse rate was significantly higher in MRD-positive patients; 3 years relapse rate in MRD-positive patients was 57.9% vs. 15.1% in MRD-negative patients. Detection of MRD in complete remission was associated with increased overall mortality (HR = 3.3; 95% CI: 1.45-7.57; p = 0.0044) and relapse (HR = 5.26; 95% CI: 2.0-14.0; p = 0.001), even after controlling for other risk factors. Our study showed that for patients in morphologic complete remission the presence of MRD predicts for significantly increased risk of relapse and reduced LFS and OS.
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Foxp3 is a nuclear transcription factor that is both a tumor suppressor factor and regulator of T-regulatory cell (Treg) function, and is a potential therapeutic target in both autoimmunity and cancer. In order to distinguish molecular pathways responsible for these separate Foxp3 functions, deletion mutants of Foxp3 proteins were transduced and analyzed for cytotoxic activity in human cancer cell lines Skov3, MDA-MB-231, MCF-7 and Jurkat. Human Foxp3 cDNA mutants were amplified and ligated to produce plasmids for direct cell transfection. Constructs were produced and confirmed by DNA sequencing. Lipofectamine 2000 was used for plasmid transfection. Foxp3 cells were then examined. The results of our experiments reveal retention of tumor suppressor function in the absence of NFAT binding and transcriptional activation required for Treg function. Our results have significant implications for the design of autoimmune and cancer therapies that target Foxp3 and Treg cells.