RESUMO
Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.
RESUMO
Acute graft-versus-host disease (aGvHD) remains a major threat to successful outcome following allogeneic hematopoietic cell transplantation though advances in prophylaxis and supportive care have been made. The aim of this study is to test whether the incidence and mortality of aGvHD have decreased over time. 102,557 patients with a median age of 47.6 years and with malignancies after first allogeneic sibling or unrelated donor (URD) transplant were studied in the following periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010 and 2011-2015. Findings: 100-day incidences of aGvHD grades II-IV decreased from 40% to 38%, 32%, 29% and 28%, respectively, over calendar time (P<0.001). In multivariate analysis URD, not in complete remission (CR) at transplant or untreated, and female donor for male recipient were factors associated with increased risk whereas the use of ATG/alemtuzumab decreased aGvHD incidence. Median follow-up was 214, 169, 127, 81 and 30 months, respectively, for the periods analyzed. Three-year-survival after aGvHD grades II-IV increased significantly from 38% to 40%, 43%, 44%, and 45%, respectively. In multivariate analysis URD, not in CR at transplant, peripheral blood as stem cell source, female donor for male recipient, and the use of ATG/alemtuzumab were associated with increased mortality whereas reduced-intensity conditioning was linked to lower mortality. Mortality increased with increasing patient age but decreased in the recent cohorts. Our analysis demonstrates that aGvHD has decreased over recent decades and also that the survival rates of patients affected with aGvHD has improved.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Alemtuzumab , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Doadores não RelacionadosRESUMO
Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1-CCR9, CXCR1-CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4-CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1-CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.
Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfócitos B/metabolismo , Centro Germinativo/metabolismo , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia , Microambiente TumoralAssuntos
Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Medidas de Resultados Relatados pelo Paciente , Doença CrônicaRESUMO
In tumor cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls, which was associated with poor clinical outcome. In corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Additionally, we investigated the effects of three CXCR4 antagonists in vitro. Therefore, we used AMD3100 (Plerixafor), AMD070 (Mavorixafor), and WKI, the niacin derivative of AMD070, which we synthesized. WK1 demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of pro-apoptotic genes of the BCL2-family in CXCR4-positive lymphoma cell lines. Finally, WK1 treatment resulted in the reduced expression of JNK-, ERK1/2- and NF-κB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.
Assuntos
Apoptose/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Aminoquinolinas , Antineoplásicos/farmacologia , Benzimidazóis , Biomarcadores , Butilaminas , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocina CXCL12/genética , Éxons , Feminino , Expressão Gênica , Compostos Heterocíclicos com 1 Anel/farmacologia , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Mutação , Estadiamento de Neoplasias , Prognóstico , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/genéticaRESUMO
BACKGROUND: Extracorporeal photopheresis (ECP) has demonstrated efficacy as second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD). The aim of our study was to analyze whether the amount of ECP-treated cells in patients with SR, aGVHD has an impact on response at 1 month. STUDY DESIGN AND METHODS: Data on white blood cells, lymphocytes, monocytes, mononuclear cells, and neutrophils, including absolute counts and counts per kilogram of body weight in ECP products from patients with aGVHD, were collected. For each cell population, the median dose per single ECP and the cumulative doses collected during the first week and the first month of treatment were compared with the response to ECP. RESULTS: In total, 99 patients underwent 1215 ECP procedures. Overall response was defined as a complete response if all signs of aGVHD resolved or a partial response if greater than 50% resolution was reached without other, additional immunosuppression. An overall response was obtained by 75% of patients, including 53% complete responses. Univariate analysis showed a correlation of lymphocytes and mononuclear cells/kg body weight for a single procedure and overall response. In logistic regression analysis, no tested variable had an influence on response. In receiver operating characteristic curve analysis, cutoffs of 8.4 × 106 /kg body weight lymphocytes and 13.9 × 106 /kg body weight mononuclear cells were associated with an overall response to ECP at 1 month with 75% sensitivity. CONCLUSION: Our results in patients with steroid-refractory aGVHD confirm that response rates to ECP are high and that certain cutoff values for lymphocytes and mononuclear cells/kg body weight in each individual procedure can predict an overall response to ECP at 1 month.
Assuntos
Contagem de Células Sanguíneas , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fotoferese , Doença Aguda , Adulto , Buffy Coat/citologia , Peso Corporal , Feminino , Doença Enxerto-Hospedeiro/sangue , Humanos , Leucemia/mortalidade , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Curva ROC , Taxa de Sobrevida , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto JovemRESUMO
Because of first-line treatment with high-dose glucocorticoids (GC), steroid-induced hyperglycemia develops frequently in patients with acute graft-versus-host disease (aGVHD), potentially affecting their outcome. We performed a retrospective analysis on 104 patients who received systemic GC for aGVHD and investigated the consequences of aberrant glucose metabolism. In particular, we focused on glucose parameters early after initiation of GC. With a median of 50 (range, 4 to 513) blood glucose measurements during GC treatment, increasing mean, median, and maximum glucose levels and the need for insulin treatment were associated with decreased overall survival (OS) in simple and multiple survival analysis. Early hyperglycemia, as defined by mean blood glucose levels >125 mg/dL during the first 3 days of GC therapy, was also found to be highly associated with adverse outcome (hazard ratio [HR], 2.5 for death; 95% confidence interval [CI], 1.3 to 4.8, and HR of 3.5 for death due to nonrelapse mortality, 95% CI, 1.7 to 7.5, in a competing risk analysis). A score based on early hyperglycemia and nonresponse to GC within 7 days allowed the identification of 3 risk groups: patients with both risk factors had an inferior OS at 5 years of 4.1% compared with 75.4% in patients with none. Patients with 1 risk factor had a 5-year OS rate of 32.0% (P = .0002 for trend). Early hyperglycemia after GC initiation is a prominent risk factor for adverse outcome in patients with aGVHD. A score based solely on early hyperglycemia and lack of response to GC can predict survival in these patients.
Assuntos
Glucocorticoides/efeitos adversos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Hiperglicemia/etiologia , Doença Aguda , Adulto , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 106 CD34+ cells/kg for a single or ≥5 × 106 CD34+ cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34+ cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34+ cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 106 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19+ and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Pré-Medicação/métodos , Adulto , Idoso , Autoenxertos/citologia , Benzilaminas , Ciclamos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation.
Assuntos
Temas Bioéticos , Seleção do Doador/ética , Seleção do Doador/métodos , Transplante de Células-Tronco Hematopoéticas/ética , Transplante de Células-Tronco Hematopoéticas/métodos , Doadores de Tecidos/ética , Adolescente , Aloenxertos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: Umbilical cord blood (UCB) is an important graft source for hematopoietic stem cell transplantation (SCT). Due to less stringent human leukocyte antigen (HLA) matching criteria compared to bone marrow or peripheral blood stem cells, UCB enables patients lacking an HLA-matched donor to receive potentially curative SCT. METHODS: We retrospectively analyzed the efficacy and safety of UCB transplantation (UCBT) at our center. RESULTS: Between June 2009 and June 2015, 27 UCBT were performed in 25 patients. Reasons for the use of UCB were lack of adequate related or unrelated stem cell donor (n = 20) and graft failure after previous SCT (n = 7). Median time to neutrophil engraftment was 22 days. Four patients experienced primary graft failure. Thirteen patients developed acute graft-versus-host disease (GVHD), whereupon 6 subsequently also developed chronic GVHD. After a median follow-up time of 19 months, 9 patients relapsed and 12 patients died. Cause of death was relapse in 8 and transplant-related events in 4 patients. Median overall survival and progression-free survival have not been reached yet. CONCLUSION: In our experience, UCBT is an alternative graft source for patients lacking a suitable related or unrelated donor and a feasible treatment option for patients experiencing graft failure after previous SCT.
Assuntos
Sangue Fetal/transplante , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/cirurgia , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas , Terapia de Salvação/métodos , Doença Aguda , Adulto , Idoso , Doença Crônica , Estudos de Viabilidade , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Chronic graft-versus-host disease (cGVHD) is a serious and frequent complication of allogeneic hematopoietic stem cell transplantation (HCT). Currently, no biomarkers for prediction and diagnosis of cGVHD are available. We performed a large prospective study focusing on noninvasive biomarkers for National Institutes of Health-defined cGVHD patients (n = 163) in comparison to time-matched HCT recipients who never experienced cGVHD (n = 64), analyzed from day 100 after HCT. In logistic regression analysis, CD19(+)CD21(low) B cells (P = .002; hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.53 to 7.17) and CD4(+)CD45RA(+)CD31(+) T cells (P < .001; HR, 3.88; 95% CI, 1.88 to 7.99) assessed on day 100 after HCT were significantly associated with subsequent development of cGVHD, independent of clinical parameters. A significant association with diagnosis of cGVHD was only observed for CD19(+)CD21(low) B cells (P = .008; HR, 3.00; 95% CI, 1.33 to 6.75) and CD4(+)CD45RA(+)CD31(+) T cells (P = .017; HR, 2.80; 95% CI, 1.19 to 6.55). CD19(+)CD21(low) B cells were found to have the highest discriminatory value with an area under the receiver operating curve of .77 (95% CI, .64 to .90). Our results demonstrate that CD19(+)CD21(low) B cells and CD4(+)CD45RA(+)CD31(+) T cells are significantly elevated in patients with newly diagnosed cGVHD.
Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Antígenos CD/genética , Antígenos CD/imunologia , Linfócitos B/patologia , Biomarcadores/análise , Linfócitos T CD4-Positivos/patologia , Doença Crônica , Feminino , Expressão Gênica , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Imunofenotipagem , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Transplante HomólogoRESUMO
The number of allogeneic hematopoietic stem cell (HSC) transplants performed globally each year continues to increase. Advances in HLA typing, better supportive care, and administration of reduced-intensity conditioning regimens allow treatment of older patients with older sibling donors. Pretransplant donor assessment and testing are very important processes affecting the quality and safety of donation. For unrelated HSC donors detailed recommendations for health assessment have been published, allowing donation only if they are unrestrictedly healthy. Eligibility criteria for related donors are less strict and vary significantly between centers. In situations where a family donor does not meet the suitability criteria for unrelated donors, involved physicians often struggle with the decision whether the matched relative is suitable for donation or not. On behalf of the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues, we intended to develop a consensus document with recommendations for donor workup and final clearance of family donors who would not be able to serve as unrelated donors because of their age or pre-existing diseases. This article covers different topics intending to support decision-making, with the goal of minimizing medical risk to the donor and protection of the recipient from transmissible diseases.
Assuntos
Transplante de Medula Óssea/métodos , Tomada de Decisão Clínica/ética , Nível de Saúde , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Doadores não Relacionados , Comitês Consultivos , Fatores Etários , Consenso , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Consentimento Livre e Esclarecido , Cooperação Internacional , Risco , Irmãos , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies.
Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Doença Enxerto-Hospedeiro/diagnóstico , Biomarcadores , Doença Crônica , Consenso , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Feminino , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Especificidade de Órgãos , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
Bronchiolitis obliterans syndrome (BOS), pathognomonic for chronic graft-versus-host disease (cGVHD) of the lung, is a progressive and often fatal complication after allogeneic hematopoietic cell transplantation (HCT). Biomarkers for the prediction and diagnosis of BOS are urgently needed to improve patients' prognosis. We prospectively evaluated B-cell subpopulations and B-cell activating factor (BAFF) in 136 patients (46 BOS, 41 no cGVHD, 49 cutaneous cGVHD) to define novel biomarkers for early diagnosis of National Institutes of Health-defined BOS diagnosed a median of 11 mo after HCT. Patients with newly diagnosed BOS had significantly higher percentages of CD19(+)CD21(low) B cells (25.5 versus 6.6%, P < .0001), BAFF (7.3 versus 3.5 ng/mL, P = .02), and BAFF/CD19(+) ratio (0.18 versus 0.02 ng/10(3) CD19(+) B cells, P 5 .007) compared with patients without cGVHD. The area under the receiver operating curve for CD19(+)CD21(low) B cells was 0.97 (95% confidence interval, 0.94-0.99) and a cutoff point >9% was optimal for diagnosing BOS in patients with first drop of pulmonary function tests with a sensitivity of 96% and a negative predictive value of 94%. Thus, elevated levels of CD19(+)CD21(low) B cells are a potential novel biomarker for HCT patients at risk for developing BOS at an early stage and could allow improvement of patient outcome.
Assuntos
Antígenos CD19/metabolismo , Linfócitos B/patologia , Bronquiolite Obliterante/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores de Complemento 3d/metabolismo , Adulto , Idoso , Fator Ativador de Células B/metabolismo , Linfócitos B/metabolismo , Biomarcadores Tumorais/metabolismo , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/metabolismo , Bronquiolite Obliterante/mortalidade , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/terapia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Prognóstico , Estudos Prospectivos , Curva ROC , Taxa de Sobrevida , Transplante Homólogo , Estados Unidos , Adulto JovemRESUMO
Autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for selected patients with multiple myeloma (MM). Many data exist on ASCT in the era of novel agents. We retrospectively analyzed 189 patients (108 males and 81 females) with biopsy-proven MM, who had received ASCT after induction therapy with either conventional chemotherapy alone or in combination with novel agents at our department. The outcomes of both groups and the risk factors for shorter survival were investigated. The most commonly used induction chemotherapy prior to ASCT was VAD (vincristine, doxorubicin and dexamethasone, 42%), followed by PAD (bortezomib, doxorubicin and dexamethasone, 21%). One-hundred and twenty-nine patients (68%) received cyclophosphamide-recombinant human granulocyte colony-stimulating factor for stem cell mobilization. No differences were observed for progression-free survival in terms of the number of transplanted CD34+ cells (p = 0.261). A trend in improved overall survival (OS) was seen for the use of novel agents when compared to conventional chemotherapy (164.3 vs. 82.0 months; p = 0.046). The International Staging System stages had a significant (p = 0.036) impact on OS. The novel agents improved OS in our patients with MM undergoing ASCT when compared to conventional chemotherapy regimens. The number of transplanted CD34+ cells had no significant impact on hematopoietic reconstitution.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/metabolismo , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Estudos Retrospectivos , Transplante Autólogo/métodos , Resultado do Tratamento , Vincristina/administração & dosagemAssuntos
Doença Enxerto-Hospedeiro , Terapia de Salvação , Doença Crônica , Humanos , Ácido MicofenólicoAssuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação , Citarabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Adulto JovemRESUMO
Graft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation causing significant morbidity and mortality. Corticosteroids are the established first-line treatment of GvHD. Patients not responding to corticosteroids have a dismal prognosis. Extracorporeal photopheresis (ECP) has objective activity in the treatment of both acute and chronic corticosteroid-refractory GvHD patients, has an excellent safety profile and is internationally well-established. ECP has been recommended by a significant number of renowned scientific organizations as an efficient treatment option for patients with GvHD. ECP has a proven corticosteroid-sparing effect and favourably impacts on survival and quality of life of responding patients.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Fotoferese/métodos , Doença Aguda , Aloenxertos , Doença Crônica , Doença Enxerto-Hospedeiro/imunologia , HumanosRESUMO
To assess current clinical practice in diagnosis and treatment of acute graft-versus-host disease (aGVHD), we performed a survey among German, Austrian, and Swiss allogeneic hematopoietic stem cell transplantation (allo-HSCT) centers. Thirty-four of 72 contacted centers (47%) completed both the diagnostic and therapeutic sections of the survey, representing 65% of allo-HSCT activity within the participating countries in 2011. Three pediatric centers answered as requested only the diagnostic part of the survey. In the presence of diarrhea and decreased oral intake after engraftment, only 4 centers (12%) do not perform any endoscopy before the start of immunosuppressive treatment. In case of a skin rash with the differential diagnosis of drug reaction, only 12 centers (35%) perform a skin biopsy up front, whereas 19 do so after failure of systemic steroids. In the presence of rapidly increasing cholestasis occurring without any other signs of aGVHD, 11 centers (32%) perform a liver biopsy up front and 14 only after failure of steroid treatment, whereas 9 centers do not perform a liver biopsy at all. Twenty centers (59%) use a percutaneous approach, 12 a transvenous approach, and 1 mini-laparoscopy for liver biopsies. First-line treatment of cutaneous aGVHD stage 1 consists of topical treatment alone in 17 of 31 responding centers (61%), whereas isolated cutaneous aGVHD stage III is treated with systemic steroids (prednisolone below 0.5 mg/kg/day n = 2, 0.5 to 1.0 mg/kg/day n = 10, above 1.0 to 2.5 mg/kg/day n = 19) without or with topical agents (steroids n = 10; calcineurin inhibitors n = 3). In gastrointestinal manifestations of aGVHD, 9 centers (29%) add topical to systemic steroids, and 3 consider topical steroids as the only treatment for mild gastrointestinal and cutaneous aGVHD. The choice of agent for second-line treatment as well as the sequence of administration are extremely heterogeneous, most likely due to a lack of convincing data published. Most frequently used are mycophenolate mofetil (n = 14) and extracorporeal photopheresis (n = 10). Our survey also demonstrates that clinicians chose salvage therapies for steroid-refractory aGVHD based on their centers' own clinical experience.