Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 266
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Am J Hematol ; 99(4): 562-569, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38314663

RESUMO

Slow platelet recovery frequently occurs after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with bone marrow graft and post-transplant cyclophosphamide (PCy)-based graft-versus-host disease (GVHD) prophylaxis. Improved platelet recovery may reduce the need for transfusions and improve outcomes. We investigated the safety and efficacy of eltrombopag, a thrombopoietin receptor agonist, at enhancing platelet recovery post-haplo-HSCT. The prospective study included patients ≥18 years of age who received haplo-HSCT with bone marrow graft and PCy. Patients received eltrombopag 300 mg/day starting on Day +5. The primary objective was to estimate platelet engraftment (>50 000/µL by Day 60). In a post hoc analysis, they were compared to a contemporary matched control group who did not receive eltrombopag. One hundred ten patients were included in the analysis (30 eltrombopag and 80 control). Seventy-three percent and 50% of patients in the eltrombopag group and control group, respectively, attained >50 000/µL platelet count by Day 60 (p = .043). No eltrombopag-related grade ≥4 adverse events were observed. Median time to platelet recovery (>20 000/µL) was 29 days with eltrombopag and 31 days for controls (p = .022), while its cumulative incidence was 90% (95% confidence interval [CI]: 78%-100%) with eltrombopag versus 67.5% (95% CI: 57%-78%) for controls (p = .014). Number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and non-relapse mortality were similar between groups. Overall, eltrombopag is safe and improves platelet recovery in patients undergoing haplo-HSCT with bone marrow graft and PCy.


Assuntos
Benzoatos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hidrazinas , Pirazóis , Humanos , Transplante de Medula Óssea/efeitos adversos , Estudos Prospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Estudos Retrospectivos
2.
N Engl J Med ; 382(6): 545-553, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32023374

RESUMO

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS: In this phase 1 and 2 trial, we administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin's lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×105, 1×106, or 1×107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. RESULTS: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. CONCLUSIONS: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).


Assuntos
Antígenos CD19 , Células Matadoras Naturais/transplante , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma não Hodgkin/terapia , Receptores de Antígenos Quiméricos/antagonistas & inibidores , Idoso , Aloenxertos , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Sangue Fetal , Vetores Genéticos , Humanos , Células Matadoras Naturais/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Retroviridae/genética , Condicionamento Pré-Transplante
3.
BMC Cancer ; 23(1): 1258, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124057

RESUMO

BACKGROUND: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). METHODS: Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. RESULTS: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0-196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. CONCLUSIONS: CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/terapia , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo , Resultado do Tratamento
4.
Int J Mol Sci ; 24(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37373245

RESUMO

Hodgkin lymphoma, a hematological malignancy of lymphoid origin that typically arises from germinal-center B cells, has an excellent overall prognosis. However, the treatment of patients who relapse or develop resistant disease still poses a substantial clinical and research challenge, even though current risk-adapted and response-based treatment techniques produce overall survival rates of over 95%. The appearance of late malignancies after the successful cure of primary or relapsed disease continues to be a major concern, mostly because of high survival rates. Particularly in pediatric HL patients, the chance of developing secondary leukemia is manifold compared to that in the general pediatric population, and the prognosis for patients with secondary leukemia is much worse than that for patients with other hematological malignancies. Therefore, it is crucial to develop clinically useful biomarkers to stratify patients according to their risk of late malignancies and determine which require intense treatment regimens to maintain the ideal balance between maximizing survival rates and avoiding late consequences. In this article, we review HL's epidemiology, risk factors, staging, molecular and genetic biomarkers, and treatments for children and adults, as well as treatment-related adverse events and the late development of secondary malignancies in patients with the disease.


Assuntos
Doença de Hodgkin , Leucemia , Segunda Neoplasia Primária , Adulto , Humanos , Criança , Doença de Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Segunda Neoplasia Primária/tratamento farmacológico , Leucemia/tratamento farmacológico
5.
Blood ; 135(6): 449-452, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-31826244

RESUMO

The optimal conditioning regimen for older patients with acute myeloid leukemia (AML) remains unclear. In this study, we compared outcomes of AML patients >60 years of age undergoing allogenic hematopoietic stem cell transplantation at our institution. All 404 consecutively treated patients received 1 of the following conditioning regimens: (1) fludarabine+melphalan 100 mg/m2 (FM100), (2) fludarabine+melphalan 140 mg/m2 (FM140), (3) fludarabine+IV busulfan AUC ≥ 5000/d × 4 d (Bu≥20000), and (4) fludarabine+IV busulfan AUC 4000/d × 4 d (Bu16000). A propensity score analysis (PSA) was used to compare outcomes between these 4 groups. Among the 4 conditioning regimens, the FM100 group had a significantly better long-term survival with 5-year progression-free survival of 49% vs 30%, 34%, and 23%, respectively. The benefit of the FM100 regimen resulted primarily from the lower nonrelapse mortality associated with this regimen, an effect more pronounced in patients with lower performance status. The PSA confirmed that FM100 was associated with better posttransplantation survival, whereas no significant differences were seen between the other regimen groups. In summary, older patients with AML benefited from a reduced-intensity conditioning regimen with lower melphalan doses (FM100), which was associated with better survival, even though it was primarily used in patients who could not receive a more intense conditioning regimen.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Bussulfano/uso terapêutico , Feminino , Humanos , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Transplante Homólogo/métodos , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
6.
Haematologica ; 107(4): 899-908, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33951890

RESUMO

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P<0.0001). Five-year PFS/OS rates were 72%/87% after vorinostat/ GemBuMel, 55%/75% after GemBuMel, 45%/61% after BEAM, and 39%/57% after BuMel (PFS: P=0.0003; OS: P<0.0001). These differences persisted within the PET-negative and PET-positive subgroups. Prior BV and vorinostat/GemBuMel were independent predictors of more favorable outcome, whereas primary refractory disease, ≥2 salvage lines, bulky relapse, B symptoms and PET-positivity at ASCT correlated independently with unfavorable outcomes. In conclusion, post-HDC/ASCT outcomes of patients with HRR classic Hodgkin lymphoma have improved over the last 15 years. Pre-ASCT BV treatment and optimized synergistic HDC (vorinostat/GemBuMel) were associated with this improvement.


Assuntos
Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
7.
Cancer ; 127(10): 1598-1605, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33471943

RESUMO

BACKGROUND: A myeloablative conditioning regimen can be safely given to older patients and those with comorbidities without increasing nonrelapse mortality (NRM) by fractionating the dose of intravenous busulfan. How this approach compares in efficacy with traditional, nonfractionated, lower dose regimens is unknown. METHODS: Outcomes were compared in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome who received either myeloablative, fractionated busulfan (f-Bu) dosed to achieve an area under the curve of 20,000 µmol per minute (f-Bu20K) over 2 weeks (n = 84) or a standard, nonfractionated, lower busulfan dose regimen of 16,000 µmol per minute (Bu16K) over 4 days (n = 78). Both groups also received fludarabine 40 mg/m2 intravenously for 4 days. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Patients in the Bu16K group who had unrelated donors also received antithymocyte globulin. The primary endpoint was progression-free survival. RESULTS: Roughly one-half of the patients were aged >65 years, approximately 40% had poor-risk cytogenetics, approximately 40% of those with AML were not in complete remission, and approximately 40% had a comorbidity index >3. At 2 years, progression-free survival was significantly improved in the f-Bu20K group compared with the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], 0.6; 95% CI, 0.4-0.8; P = .004). This was because of a significant reduction in progression (34% vs 59%, respectively; HR, 0.5; 95% CI, 0.3-0.8; P = .003) without any increase in NRM (21% vs 15%, respectively; HR, 1.4; 95% CI, 0.7-3; P = .3), which resulted in improved overall survival (51% vs 31%, respectively; HR, 0.6; 95% CI, 0.3-0.9; P = .01). CONCLUSIONS: A myeloablative, fractionated busulfan regimen reduces relapse and improves survival without increasing NRM in older patients with AML and myelodysplastic syndrome.


Assuntos
Bussulfano , Leucemia Mieloide Aguda , Agonistas Mieloablativos , Síndromes Mielodisplásicas , Condicionamento Pré-Transplante , Idoso , Bussulfano/administração & dosagem , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Agonistas Mieloablativos/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
8.
N Engl J Med ; 378(1): 35-47, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29298160

RESUMO

BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. RESULTS: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).


Assuntos
Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Escleroderma Sistêmico/terapia , Adolescente , Adulto , Idoso , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunossupressores/efeitos adversos , Infecções/etiologia , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/mortalidade , Condicionamento Pré-Transplante , Transplante Autólogo , Adulto Jovem
9.
Cytotherapy ; 23(11): 1029-1035, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34247985

RESUMO

BACKGROUND AIMS: Umbilical cord blood is an established source of stem cells in patients with hematologic malignancies who do not have HLA-compatible matched related or unrelated donors. The success of an umbilical cord blood transplant depends on the dose of total nucleated and CD34+ cells infused. Therefore, collecting, banking and listing high-quality cord blood units with high total nucleated and CD34+ cell dose are essential. METHODS: Here the authors describe their cord blood bank's novel collection technique, which involves both in utero and ex utero collection of a single cord blood unit. The authors also evaluated maternal, neonatal and collection parameters that may impact the cell dose. RESULTS: Maternal gestational age and race, and neonatal weight and sex correlated with the total nucleated cell dose. CONCLUSIONS: The optimized collection of umbilical cord blood is critical for its use as a source of stem cells for transplantation.


Assuntos
Bancos de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Criopreservação , Família , Sangue Fetal , Idade Gestacional , Humanos
10.
Eur J Haematol ; 107(6): 634-641, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34431142

RESUMO

OBJECTIVES: Calcineurin inhibitor (CNI) use for acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT) recipients has been associated with toxicities. Toxicities may be managed by converting CNI to sirolimus as often done in solid organ transplantation. This study aimed to characterize allo-HCT patients who completely transitioned from tacrolimus to sirolimus and evaluate the incidence of aGVHD within 100 days post-transition, overall survival (OS), and incidence of relapse. METHODS: Safety and efficacy data were collected at baseline and at day 30 and 90 post-transition from tacrolimus to sirolimus and at one-year post-HCT. RESULTS: Most patients who transitioned had acute leukemia, received a matched unrelated donor allo-HCT, and transitioned due to nephrotoxicity or neurotoxicity. The resolution rate was 83% and 48% in the nephrotoxicity group, 78% and 61% in the neurotoxicity group, 33% and 33% in the group that developed both nephrotoxicity and transplant-associated thrombotic microangiopathy at 30 and 90 days of assessments, respectively. Patients who transitioned before day 55 post-allo-HCT were more likely to develop new or worsening aGVHD. The one-year OS and relapse rates were 37% and 20%, respectively. CONCLUSIONS: The conversion from tacrolimus to sirolimus demonstrates promising resolution of acute toxicities; however, overall mortality remains high.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/administração & dosagem , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Adulto Jovem
11.
Acta Haematol ; 144(1): 74-81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32604096

RESUMO

Acute myeloid leukemia (AML) patients not in remission and beyond first or second complete remission are considered allogeneic stem cell transplant (SCT) candidates. We present 361 patients who underwent SCT from matched related or unrelated donors between 2005 and 2013. The purpose was to identify a subgroup of patients with active disease at the time of transplant that benefit. Cox proportional hazards regression analysis was used for univariate and multivariate analyses to predict overall survival (OS). Variables considered were age, sex, SWOG cytogenetic risk group, bone marrow (BM) and peripheral blood (PB) blast percentage, regimen intensity, and type of AML. At a median of 26 months after transplantation, OS, progression-free survival (PFS), non-relapse mortality, and relapse rates were 26, 24, 23, and 48%, respectively. In a univariate analysis, risk cytogenetics (p < 0.001) and BM blasts >4% (p = 0.006) or any blasts in PB (p < 0.001) indicated worse OS. In a multivariate analysis, patients with <5% BM blasts or absence of circulating blasts and good or intermediate risk cytogenetics had significantly superior OS (46%), PFS (44%), and disease progression at 3 years. Based on these findings, patients not in remission with good or intermediate risk cytogenetics and low blast counts should be considered for SCT.


Assuntos
Medula Óssea/patologia , Aberrações Cromossômicas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais , Biópsia , Análise Citogenética , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
12.
Dermatol Online J ; 27(6)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34387060

RESUMO

Nontuberculous mycobacteria are pathogens with diverse manifestations in immunocompromised hosts. The lesser-known Mycobacterium haemophilum usually causes cutaneous infection. Diagnosis is challenging but is aided by molecular testing and multidisciplinary communication. We present an immunocompromised patient with disseminated cutaneous mycobacterial infection with digital tenosynovitis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções por Mycobacterium não Tuberculosas/patologia , Complicações Pós-Operatórias/patologia , Feminino , Humanos , Pessoa de Meia-Idade
13.
Biol Blood Marrow Transplant ; 26(8): 1439-1445, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32438043

RESUMO

Optimal conditioning regimens for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplant are not known. Likewise, the role of dose intensity is not clear. We conducted a nonrandomized, prospective, phase II trial using low-dose, later escalated to high-dose (myeloablative conditioning), busulfan with fludarabine (Bu-Flu) in myelofibrosis patients up to age 74 years. The first 15 patients received i.v. busulfan 130 mg/m2/day on days -3 and -2 ("low dose"); 31 patients received high-dose conditioning, either 100 mg/m2/day (days -5 to -2; n = 4) or pharmacokinetic-guided area under the curve of 4000 µmol/min (days -5 to -2; n = 27). The primary endpoint was day 100 nonrelapse mortality (NRM). Median age was 58 years (interquartile range [IQR], 53-63). Dynamic international prognostic scoring system-plus was intermediate (n = 28) or high (n = 18). Donors were related (n = 19) or unrelated (n = 27). Cumulative incidence of NRM was 9.7% (95% confidence interval [CI], 0-20.3) at day 100 and at 3 years in the high-dose group and 0% in the low-dose group at day 100, which increased to 20% (95% CI, 0-41.9) at 3 years. With a median follow-up of 5.1 years (IQR, 3.8-6), 3-year relapse was 32.3% (95% CI, 15.4-49.1) in high dose versus 53.3% (95% CI, 26.6-80.1) in low dose. Event-free survival was 58% (95% CI, 43-78) versus 27% (95% CI, 12-62), and overall survival was 74% (95% CI, 60-91) versus 60% (95% CI, 40-91). In multivariate analysis, high-dose busulfan had a trend toward lower relapse (hazard ratio, .44; 95% CI, .18-1.07; P = .07), with no impact on NRM. Intensifying the Bu-Flu regimen using pharmacokinetic-monitoring appears to be promising in reducing relapse without increasing NRM.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Mielofibrose Primária , Idoso , Bussulfano , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Mielofibrose Primária/terapia , Estudos Prospectivos , Condicionamento Pré-Transplante , Vidarabina/uso terapêutico
14.
Biol Blood Marrow Transplant ; 26(6): 1077-1083, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31786242

RESUMO

In this retrospective analysis, we evaluated the impact of age on the outcome of patients with multiple myeloma who received an autologous hematopoietic stem cell transplantation (auto-HCT) at our institution. A total of 1128 patients were divided into the older (>70 years; 182 [16%]) and the younger (≤70 years; 946 [84%]) groups. Compared with the younger cohort, older patients had a higher International Staging System (ISS) stage (ISS-II, 57 [31%] versus 215 [23%]; ISS-III, 52 [28%] versus 211 [22%]; P = .01), higher use of reduced-dose melphalan as a conditioning regimen (140 mg/m², 59 [32%] versus 29 [3%]; P < .001), and a higher comorbidity index (median, 3 versus 2; P = .01). Nonrelapse mortality at 1 year after auto-HCT was significantly higher in older patients (7 [4%] versus 9 [1%]; hazard ratio [HR], 4.1; P = .005). Complete remission rates after auto-HCT for the older and the younger groups were 41% and 46%, respectively. With a median follow-up of 52 months, the 5-year progression-free survival (PFS) was 24% (95% confidence interval [CI], 17% to 32%) and 37% (95% CI, 33% to 40%) in the older and younger groups, respectively (HR, 1.3; P = .02). Five-year OS for the older and younger groups was 56% (95% CI, 47% to 64%) and 73% (95% CI, 70% to 76%; P < .001), respectively. Older age emerged as one of the predictors of shorter OS but not PFS in the multivariate classification and regression tree analysis. In conclusion, age ≥70 years was associated with shorter PFS and OS in patients with multiple myeloma who underwent an auto-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento
15.
Biol Blood Marrow Transplant ; 26(4): 665-671, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31881283

RESUMO

The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p-, or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p- and the control group, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p- group and 56% and 86% for the control group. Patients in the 1q+/1p- group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p- alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p- abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p- patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p-.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Cromossomos , Humanos , Hibridização in Situ Fluorescente , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Pontuação de Propensão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
16.
Blood ; 131(11): 1248-1257, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29386198

RESUMO

We investigated the impact of donor-recipient HLA-DPB1 matching on outcomes of allogeneic hematopoietic stem cell transplantation with in vivo T-cell depletion using antithymocyte globulin (ATG) for patients with hematological malignancies. All donor-recipient pairs had high-resolution typing for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DRB3/4/5 and were matched at HLA-A, HLA-B, HLA-C, and HLA-DRB1. HLA-DPB1 mismatches were categorized by immunogenicity of the DPB1 matching using the DPB T-cell epitope tool. Of 1004 donor-recipient pairs, 210 (21%) were DPB1 matched, 443 (44%) had permissive mismatches, 184 (18%) had nonpermissive mismatches, in graft-versus-host (GVH) direction, and 167 (17%) had nonpermissive mismatches in host-versus-graft (HVG) direction. Compared with HLA-DPB1 permissive mismatched pairs, nonpermissive GVH mismatched pairs had the highest risk for grade II to IV acute graft-versus-host disease (aGVHD) (hazard ratio [HR], 1.4; P = .01) whereas matched pairs had the lowest risk (HR, 0.5; P < .001). Grade III to IV aGVHD was only increased with HLA-DPB1 nonpermissive GVH mismatched pairs (HR, 2.3; P = .005). The risk for disease progression was lower with any HLA-DPB1 mismatches, permissive or nonpermissive. However, the favorable prognosis of HLA-DPB1 mismatches on disease progression was observed only in peripheral blood stem cell recipients who were in the intermediate-risk group by the Disease Risk Index (HR, 0.4; P = .001) but no other risk groups. Our results suggest avoidance of nonpermissive GVH HLA-DPB1 mismatches for lowering the risk for grade II to IV and III to IV aGVHD. Permissive or nonpermissive HVG HLA-DPB1 mismatches may be preferred over HLA-DPB1 matches in the intermediate-risk patients to decrease the risk for disease progression.


Assuntos
Cadeias HLA-DRB1 , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Depleção Linfocítica , Linfócitos T , Doença Aguda , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
17.
Biol Blood Marrow Transplant ; 25(3): 505-514, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30308325

RESUMO

The outcome of persons > 65 years with acute myeloid leukemia (AML) is poor. A transplant from an HLA-identical sibling or an HLA-matched unrelated donor can cure some of these patients but is associated with a substantial transplant-related mortality and a high relapse risk. We analyzed 185 subjects > 65 years with high-risk AML receiving conventional (n = 42) or reduced-intensity (n = 143) pretransplant conditioning and a transplant from an HLA-identical sibling (n = 66) or a 10/10 loci HLA-matched unrelated donor (n = 119). Two-year survival was 37%. Subjects with serious adverse events during before chemotherapy for their leukemia had a poor outcome after stem cell transplantation. Patients who had active leukemia or measurable residual disease (MRD) before transplantation had a worse outcome. Delayed hematologic recovery after induction or consolidation chemotherapy, high-risk AML genetics, donor-recipient HLA-DRß3/4/5-DP mismatches, and history of cardiovascular disease were also correlated with survival in multivariate analyses. The 57 MRD-negative patients with few other adverse prognostic factors had an excellent outcome (2-year overall survival, 76%), whereas the 58 patients with detectable leukemia and more than 1 other additional factor fared poorly (2-year overall survival, 8%). These data indicate it is possible to identify persons > 65 years with high-risk AML likely to benefit from an allotransplant. Validation of this prediction is needed.


Assuntos
Fatores Etários , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/terapia , Idoso , Feminino , Histocompatibilidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Mortalidade , Prognóstico , Recidiva , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo
18.
Biol Blood Marrow Transplant ; 25(5): 1039-1044, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30639822

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with multiple myeloma, as it provides a graft-versus-myeloma effect alongside a myeloma-free graft. Although reduced-intensity conditioning regimens decrease nonrelapse mortality (NRM), there is a paucity of data with regard to the ideal conditioning regimen in myeloma. We conducted a retrospective comparison of 3 different preparative regimens used for allo-HCT for multiple myeloma at our institution in recent clinical trials: busulfan/fludarabine (BuFlu), fludarabine/melphalan 100 mg/m2 (FM100), and fludarabine/melphalan 140 mg/m2 (FM140). NRM, progression-free survival (PFS) at 3 years, and overall survival (OS) at 3 years were the primary endpoints. Secondary endpoints included time to engraftment, and the incidence of grades II through IV acute graft-versus-host disease and chronic graft-versus-host disease. A total of 73 patients received allo-HCT with these regimens. NRM at 3 years was seen in 3 (21%), 5 (28%), and 6 (24%) patients in the BuFlu, FM100, and FM140 groups, respectively. Three-year PFS in the BuFlu, FM100, and FM140 groups was 16% (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.6 to 2.1), 26% (HR, 0.6; 95% CI, 0.3 to 1.2), and 11% (reference), respectively. Three-year OS in the BuFlu, FM100, and FM140 groups was 39% (HR, 1.1; 95% CI, 0.5 to 2.2), 43% (HR, 0.7; 95% CI, 0.3 to 1.4), and 32% (reference), respectively. High-risk cytogenetics and relapsed disease prior to allo-HCT were found to be independent predictors of inferior OS on multivariate analysis, with a HR of 2.1 (P = .02) and 2.6 (P = .004), respectively. In contrast, the preparative regimen did not emerge as a predictor of PFS or OS. Durable clinical remission can be achieved in 11% to 25% of patients with multiple myeloma with the use of allo-HCT without any significant difference in the safety or efficacy of the conditioning regimen. High-risk cytogenetics and relapsed disease prior to transplant were associated with inferior PFS and OS.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Bussulfano/uso terapêutico , Butirofenonas/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
19.
Biol Blood Marrow Transplant ; 25(7): 1340-1346, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30763728

RESUMO

We analyzed 186 patients with lymphoma who underwent allogeneic stem cell transplantation (ASCT) with fludarabine-melphalan (FM) conditioning and different types of donors (25 haploidentical [HD], 98 matched unrelated [MUD], and 63 matched related [MRD]) at our institution between September 2009 and January 2018. Patients received fludarabine 160 mg/m2 (40 mg/m2/day for 4 days) in combination with 1 dose of melphalan 140 mg/m2 (FM140) or 100 mg/m2 (FM100). Engraftment was similar among the 3 groups (92%, 89%, and 98%, respectively; P = .7). The 6-month cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 4% in the HD group, 14% in the MUD group, and 8% in the MRD group (P not significant), and the respective 3-year cumulative incidence of chronic GVHD was 5%, 16%, and 26% (P not significant). The respective 3-year nonrelapse mortality and relapse rates were 31%, 32%, and 10% (HD versus MUD, P = .9; HD versus MRD, P = .02) and 15%, 21%, and 39% (HD versus MUD, P = .4; HD versus MRD, P = .04). At 3 years, progression-free survival (PFS) was 59%, 44%, and 46% (P not significant); overall survival (OS) was 52%, 54%, and 67% (P not significant); and GVHD-free, relapse-free survival was 39%, 31%, and 24% (P not significant). No differences in the 3-year PFS (57% versus 43%; P = .3) and OS (64% versus 58%; P = .7) were seen between patients receiving FM100 and those receiving FM140. Our data demonstrate that in patients with lymphoma, ASCT with HD transplants have similar outcomes as ASCT with HLA-matched transplants, and the FM100 conditioning regimen appears to be at least as effective as the FM140 regimen.


Assuntos
Doença Enxerto-Hospedeiro , Linfoma , Melfalan/administração & dosagem , Transplante de Células-Tronco , Doadores de Tecidos , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Humanos , Incidência , Linfoma/mortalidade , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
20.
Transfusion ; 59(11): 3519-3524, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31587288

RESUMO

BACKGROUND: In the past, conventional treatment strategies for transplant-associated thrombotic microangiopathy (TA-TMA) have not proven to be very effective. Recently, eculizumab which is a humanized monoclonal antibody that works as a terminal complement inhibitor has demonstrated promise in the treatment landscape of TA-TMA. METHODS AND MATERIALS: This was a single-center retrospective analysis of 20 consecutive adult patients with TA-TMA: 10 patients who received conventional therapy and 10 patients who received eculizumab-based therapy. These patients had undergone allogeneic HSCT at MD Anderson Cancer Center between August 2011 and September 2016. RESULTS: When comparing the treatment outcomes in the two cohorts, none of the patients in the conventional therapy group obtained a hematologic or complete response according to our response criteria whereas seven patients in the eculizumab group achieved a hematologic response with one patient achieving a complete response with organ recovery. In addition, overall survival at the end of assessment was 60% in the eculizumab cohort and 30% in the conventional cohort. One major difference in practice at our institution versus previously published studies is the management of immunosuppression. In a majority of patients, tacrolimus was continued or transitioned to sirolimus for GVHD prophylaxis. CONCLUSION: Response rates and survival were improved for patients who were transitioned to sirolimus, so a two-pronged approach of inhibiting complement along with providing an alternative effective immunosuppressive agent may be beneficial in the treatment of early onset TA-TMA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Microangiopatias Trombóticas/tratamento farmacológico , Adolescente , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/mortalidade , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA