RESUMO
BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. AIM: To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. METHODS: We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. RESULTS: Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). CONCLUSION: The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.
Assuntos
Expressão Gênica/genética , Doença Enxerto-Hospedeiro/metabolismo , Interferons/genética , Lúpus Eritematoso Sistêmico/metabolismo , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Dermatopatias/patologiaRESUMO
Several studies reported that patients with acute myeloid leukemia (AML) who remain in long-term remission after allogeneic or autologous transplant have a shorter life expectancy, compared to the general population. However, little is known about the life expectancy of adult long-term survivors of AML who were treated with chemotherapy alone without a transplant and there have been no comparisons with survival among the general population. The current study indicates that the life expectancy of AML patients who achieved and maintained CR for at least 3 years is shorter than expected for age in the US population. This was observed also in patients who did not undergo a transplant including those who have not relapsed during the entire long follow-up period. Thus, late relapse does not explain why patients without transplants have a shortened life expectancy. Taken together, these data strongly suggest that prior chemotherapy for the underlying AML is at least a major contributing factor for the known shortened life expectancy post-transplant.
RESUMO
Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Estado Civil , Qualidade de VidaAssuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Indução de Remissão , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
The absence of a graft-versus-malignancy (GVM) effect may be responsible for the higher relapse rate seen after autologous hematopoietic cell transplantation (auto-HCT) compared with allogeneic hematopoietic cell transplantation (allo-HCT). Acute GVHD developing after allo-HCT, however, is associated with significant morbidity and mortality. An autoimmune syndrome similar to acute GVHD has been reported to occur after auto-HCT and has been termed the 'auto-aggression' syndrome or autologous GVHD (auto-GVHD). Auto-GVHD tends to be milder than classical GVHD, most commonly involves the skin (rarely the gastrointestinal tract, liver or both) and often is self-limited. Auto-GVHD has been reported to occur both spontaneously and in subjects receiving post transplant immune modulation with CsA, IFN-gamma or the combination. The development of auto-GVHD depends upon the derangement of self tolerance either through administration of post transplant CsA, depletion of regulatory T cells following the preparative chemoradiotherapy or both. Self-reactive CD8(+) T cells paradoxically are able to recognize a self peptide antigen presented by MHC class II molecules and appear to mediate the syndrome. Many clinical trials have been performed using CsA with or without IFN-gamma in an attempt to induce auto-GVHD. While many patients do indeed develop the syndrome, any associated anti-tumor effect remains questionable to date. New strategies to exploit auto-GVHD and enhance a GVM effect such as through the depletion of regulatory T cells or through use of newer immunomodulatory agents may improve the efficacy of auto-HCT.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Efeito Enxerto vs Tumor/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Animais , Antivirais/uso terapêutico , Doenças Autoimunes/induzido quimicamente , Ensaios Clínicos como Assunto , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Neoplasias Hematológicas/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunidade Celular/imunologia , Imunossupressores/uso terapêutico , Interferon gama/uso terapêutico , Camundongos , Modelos Animais , Tolerância a Antígenos Próprios/efeitos dos fármacos , Transplante AutólogoRESUMO
Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic cell transplant (HCT) recipients. Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction post transplant. Elevated pretransplant ferritin levels have been reported to increase the risk of nonrelapse mortality following HCT and might influence the risk of acute and chronic GVHD. Serum ferritin is sensitive but not specific for iron overload and is a poor predictor of body iron burden. Estimation of hepatic iron content with a liver biopsy or magnetic resonance imaging should be considered prior to initiating therapy for post transplant iron overload. A subgroup of transplant survivors with mild iron overload and no end-organ damage may not need therapy. Phlebotomy is the treatment of choice with iron-chelation therapy reserved for patients not eligible for phlebotomy. Natural history, evolution and treatment of iron overload in transplant survivors have not been adequately investigated and more studies are needed to determine its impact on short-term and long-term morbidity and mortality.
Assuntos
Transfusão de Eritrócitos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sobrecarga de Ferro/etiologia , Ferritinas/sangue , Ferritinas/fisiologia , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/terapia , FlebotomiaRESUMO
The aim of this study was to identify risk factors associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116 patients underwent ASCT in 1989-2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score <90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of PFS in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30-69) and 34% (95% CI 22-47) respectively. The 5-year probability of PFS in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3-30). PFS rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials.
Assuntos
Agonistas Mieloablativos/uso terapêutico , Sarcoma de Ewing/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Criança , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/secundário , Análise de Sobrevida , Transplante AutólogoRESUMO
For adults with high-risk or recurrent ALL who lack a suitable sibling donor, the decision between autologous (Auto) and unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) is difficult due to variable risks of relapse and treatment-related mortality (TRM). We analysed data from two transplant registries to determine outcomes between Auto and URD HSCT for 260 adult ALL patients in first (CR1) or second (CR2) CR. All patients received a myeloablative conditioning regimen. The median follow-up was 77 (range 12-170) months. TRM at 1 year post transplant was significantly higher with URD HSCT; however, there were minimal differences in TRM according to disease status. Relapse was higher with Auto HSCT and was increased in patients transplanted in CR2. Five-year leukemia-free (37 vs 39%) and overall survival (OS) rates (38 vs 39%) were similar for Auto HSCT vs URD HSCT in CR1. There were trends favoring URD HSCT in CR2. The long-term follow-up in this analysis demonstrated that either Auto or URD HSCT could result in long-term leukaemia-free survival and OS for adult ALL patients. The optimal time (CR1 vs CR2) and technique to perform HSCT remains an important clinical question for adult ALL patients.
Assuntos
Transplante de Medula Óssea/métodos , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.
Assuntos
Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Efeito Enxerto vs Tumor , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Metástase Neoplásica , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Transplante HomólogoRESUMO
Evaluation of time to event outcomes usually is examined by the Kaplan-Meier method and Cox proportional hazards models. We developed a modified statistical model based on histologic grade and other variables to describe the time-dependent outcome for autologous stem cell transplant (autotransplant) performed for non-Hodgkin's lymphoma (NHL) based on histologic grade and other variables. One hundred and fourteen relapsed or refractory NHL patients were treated using BCNU 600 mg/m2, etoposide 2400 mg/m2, and cisplatin 200 mg/m2 IV followed by autotransplant. Median age was 53.5 (range: 25-70) years, 78 patients had aggressive NHL and 36 indolent NHL. Seventy-five patients received involved-field radiotherapy just prior to transplant. At a median follow-up of 33 (range: 3 to 118) months, the estimated 5-year Kaplan-Meier probabilities of overall survival and disease-free survival were 61% and 51%, respectively. Cox proportional hazards model analysis showed that proportionality did not hold for lymphoma grade, indicating that the relationship between the grade and disease-free survival differed over time. By piece-wise Cox model, the relative risk for experiencing relapse or death after 1 year in patients with indolent compared with patients with aggressive NHL was 2.81 (p=0.019) with 95% confidence interval (1.19, 6.65). The time-dependent effect of lymphoma grade on disease-free survival suggests the need for early (within first year) incorporation of novel therapeutic approaches in management of patients with indolent NHL undergoing autotransplant.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco , Adulto , Idoso , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Modelos de Riscos Proporcionais , Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
We have examined the ability of extracellular ATP to elicit intracellular Ca2+ mobilization in a broad range of human leukocytes at particular stages of hematopoietic differentiation. The average cytosolic [Ca2+] in various leukocyte populations was measured in Fura 2-loaded cell suspensions while the cytosolic [Ca2+] in individual, Indo 1-loaded leukocytes was assayed by flow cytometric methods. Utilizing normal blood- and marrow-derived cells, human leukemic cell lines, and mononuclear cell fractions derived from the blood of patients with various leukemias, we have found that ATP-induced Ca2+ mobilization appears restricted to leukocytes of neutrophil/monocyte ontogeny. Significant ATP-induced increases in cytosolic [Ca2+] were observed in neutrophils, monocytes, and myeloid progenitor cells as immature as myeloblasts, but not in lymphocytes. Extensive characterization of the ATP-induced changes in [Ca2+] observed in the HL-60 promyelocytic cell line have indicated these Ca2+-mobilizing effects of ATP can be correlated with an activation of inositol phospholipid breakdown via the occupation of P2-purinergic receptors Significantly, of the various agonists (FMLP, platelet-activating factor, LTB4, and ATP) which elicit equivalent and maximal Ca2+ mobilization in mature neutrophils and monocytes, ATP was the most efficacious stimulant of Ca2+ mobilization in immature neutrophil/monocyte precursors. Thus, expression of putative P2-purinergic receptors for ATP appears to precede expression of other receptor types known to activate the inositol phospholipid signaling cascades in terminally differentiated phagocytes.
Assuntos
Trifosfato de Adenosina/fisiologia , Cálcio/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Leucócitos Mononucleares/metabolismo , Neutrófilos/metabolismo , Fagócitos/metabolismo , Medula Óssea , Linhagem Celular , Transformação Celular Neoplásica/metabolismo , Citosol/metabolismo , Espaço Extracelular/fisiologia , Humanos , Leucemia Mieloide/metabolismo , Células-Tronco Neoplásicas/metabolismoRESUMO
The genetic defect underlying paroxysmal nocturnal hemoglobinuria (PNH) has been shown to reside in PIGA, a gene that encodes an element required for the first step in glycophosphatidylinositol anchor assembly. Why PIGA-mutated cells are able to expand in PNH marrow, however, is as yet unclear. To address this question, we compared the growth of affected CD59(-)CD34(+) and unaffected CD59(+)CD34(+) cells from patients with that of normal CD59(+)CD34(+) cells in liquid culture. One hundred FACS-sorted cells were added per well into microtiter plates, and after 11 days at 37 degrees C the progeny were counted and were analyzed for their differentiation pattern. We found that CD59(-)CD34(+) cells from PNH patients proliferated to levels approaching those of normal cells, but that CD59(+)CD34(+) cells from the patients gave rise to 20- to 140-fold fewer cells. Prior to sorting, the patients' CD59(-) and CD59(+)CD34(+) cells were equivalent with respect to early differentiation markers, and following culture, the CD45 differentiation patterns were identical to those of control CD34(+) cells. Further analyses of the unsorted CD59(+)CD34(+) population, however, showed elevated levels of Fas receptor. Addition of agonist anti-Fas mAb to cultures reduced the CD59(+)CD34(+) cell yield by up to 78% but had a minimal effect on the CD59(-)CD34(+) cells, whereas antagonist anti-Fas mAb enhanced the yield by up to 250%. These results suggest that expansion of PIGA-mutated cells in PNH marrow is due to a growth defect in nonmutated cells, and that greater susceptibility to apoptosis is one factor involved in the growth impairment.
Assuntos
Células da Medula Óssea/fisiologia , Hemoglobinúria Paroxística/genética , Proteínas de Membrana/genética , Células-Tronco/fisiologia , Receptor fas/metabolismo , Antígenos CD34 , Medula Óssea/cirurgia , Células da Medula Óssea/citologia , Antígenos CD59 , Diferenciação Celular , Separação Celular , Citaferese , Glicosilfosfatidilinositóis/biossíntese , Hemoglobinúria Paroxística/etiologia , Humanos , Fenótipo , Células-Tronco/citologiaRESUMO
Transplantation-associated thrombotic microangiopathy (TA-TMA) is an infrequent but devastating syndrome that occurs in allogeneic hematopoietic stem cell transplant recipients, and is associated with a variety of transplantation-related factors, including conditioning regimens, immunosuppressive agents, GVHD and opportunistic infections. Progress in managing this condition has been hampered by lack of a consensus definition and poor understanding of the pathophysiology of the disorder. Two different groups recently have proposed consensus definitions, yet they fail to distinguish the primary syndrome from the secondary causes, such as a variety of infections, medication exposure or other conditions. Increasing evidence suggests that TA-TMA is a multifactorial disorder that is distinct from thrombotic thrombocytopenic purpura (TTP), and likely represents the final common pathway of a number of endothelial cell insults. TA-TMA responds poorly to conventional treatment for TTP, including plasma exchange, but newer agents, including daclizumab and defibrotide show promise. In addition, other agents known to modify endothelial responses to injury, including statins, prostacyclin analogues, endothelin-receptor antagonists and free radical scavengers, may lead to improved outcomes for patients affected by this disorder.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Trombose/etiologia , Transplante Homólogo/efeitos adversos , Adulto , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/etiologia , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia , Fatores de Risco , Trombose/diagnóstico , Trombose/terapiaRESUMO
Currently, granulocyte colony stimulating factor (G-CSF) remains the standard mobilizing agent for peripheral blood stem cell (PBSC) donors, allowing the safe collection of adequate PBSCs from the vast majority of donors. However, G-CSF mobilization can be associated with some significant side effects and requires a multi-day dosing regimen. The other cytokine approved for stem cell mobilization, granulocyte-macrophage colony stimulating factor (GM-CSF), alters graft composition and may reduce the development of graft-versus-host disease, but a significant minority of donors fails to provide sufficient CD34+ cells with GM-CSF and some experience unacceptable toxicity. AMD3100 is a promising new mobilizing agent, which may have several advantages over G-CSF for donor mobilization. As it is a direct antagonist of the interaction between the chemokine stromal-derived factor-1 and its receptor CXCR4, AMD3100 mobilizes PBSCs within hours rather than days. It is also well tolerated, with no significant side effects reported in any of the clinical trials to date. Studies of autologous and allogeneic transplantation of AMD3100 mobilized grafts have demonstrated prompt and stable engraftment. Here, we review the current state of stem cell mobilization in normal donors and discuss novel strategies for donor stem cell mobilization.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Benzilaminas , Transplante de Medula Óssea , Ciclamos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Compostos Heterocíclicos/efeitos adversos , Compostos Heterocíclicos/farmacologia , Humanos , Proteínas Recombinantes , Segurança , Doadores de Tecidos , Transplante HomólogoRESUMO
High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard approach for chemosensitive, relapsed aggressive non-Hodgkin's lymphoma (NHL). Various conditioning regimens have been used as treatment before ASCT and disease-free (DFS) and overall survival (OS) rates range from 34 to 60% and 26 to 46%, respectively. To date, few comparative randomized trials have been performed and no regimen has demonstrated superiority to another. Reduction of disease relapse remains the major hurdle for improving patient outcome and in vitro and in vivo purging of lymphoma cells has not necessarily enhanced results. Rituximab pre-mobilization and post-transplant appear to provide better response rates with OS approaching 87-91% at 2-3 years. Newer approaches with radioimmunotherapy may raise DFS to 78% and OS to 93%, albeit with short follow-up. Advances in the conditioning regimens and supportive care have reduced transplant-related mortality to less than 10%. In this review we discuss commonly utilized conditioning regimens, describe their pros and cons and address purging and present conditioning strategies. Owing to the poor outcome with conventional chemotherapy in mantle cell, Burkitt's and T-cell lymphoma, we propose the standard approach of front-line ASCT for these high-risk lymphoma patients. Finally, we will present novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity, to improve the outcome of ASCT in NHL patients.
Assuntos
Transplante de Medula Óssea , Linfoma não Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Humanos , RecidivaRESUMO
Acute myeloid leukaemia in the elderly is a disease with distinct biological properties, commonly associated with leukaemic cell treatment resistance and with an increased number of high-risk features, including concomitant myelodysplasia and poor-risk cytogenetic abnormalities such as monosomy 5 and 7. Complete remission rates after standard induction chemotherapy in patients above age 60 years are less than 50%, with long-term survival rates below 10%. Post-remission stem cell transplant therapies have not been studied extensively. Autologous transplants can result in an acceptable 3-year leukaemia-free survival rate of up to 47%, yet this procedure is applicable only to a small minority of patients. Myeloablative allogeneic transplants similarly show feasibility in selected few patients and in general are very toxic. Non-myeloablative allogeneic transplants are associated with reduced toxicity, but are plagued by an increased relapse rate. The latter strategy appears promising, but must be validated in larger, multi-centre prospective trials, in which outcomes are compared to non-transplant approaches.
Assuntos
Leucemia Mieloide/epidemiologia , Leucemia Mieloide/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide/mortalidade , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
Allogeneic stem cell transplantation for acute myeloid leukemia (AML) using reduced-intensity conditioning (RIC) is based on the strategy of attaining donor cell engraftment with immunosuppressive agents. This approach, which relies predominantly on donor effector cells for anti-leukemic or graft-versus-leukemia effect, is being used with increased frequency. Treatment-related mortality appears less with RIC than that observed with conventional myeloablative regimens. Available data support the fact that a myeloablative regimen is not required for successful engraftment and some patients appear to be cured of their disease. Despite the plethora of clinical reports, however, no prospective studies have been conducted that establish this procedure as the preferred option in AML. On the other hand, patients formerly excluded from a myeloablative procedure such as the 'elderly' and those with significant comorbid conditions, often may be RIC transplant candidates. By using prospective controlled clinical trials, we will determine whether these encouraging RIC data are applicable to a nonselect population of AML. The transplant community now is poised to design and complete investigations to ascertain the true role of RIC in the treatment of AML.
Assuntos
Leucemia Mieloide/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Ensaios Clínicos como Assunto , HumanosRESUMO
Patients with acute myeloid leukemia (AML) who fail to achieve complete remission (CR) have a dismal prognosis. Although data suggest that durable remissions can be achieved in approximately 30% of patients with refractory or relapsed AML after allogeneic hematopoietic cell transplantation (HCT), only a small fraction of those patients are offered this therapeutic option. Importantly, patients with primary refractory AML have distinctly better outcomes following allogeneic HCT than those with refractory relapse. Access to suitable donors could be one of the main barriers in these situations. However, with recent developments in the field of allogeneic HCT, such as alternative donor sources, high-resolution HLA-typing, reduced intensity conditioning regimens and improvements in supportive care, this approach has the potential to offer long-term survival for patients with refractory and relapsed AML and should be considered as early after diagnosis as possible. Incorporating novel agents into the conditioning regimen or as post-transplant maintenance therapy could further improve outcomes and render older or medically infirm patients with refractory or relapsed AML eligible for allogeneic HCT. In this review, we summarize existing data on allogeneic HCT in patients with refractory or relapsed AML and explore novel approaches with the potential to improve outcomes in this patient population.