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1.
Ann Nucl Med ; 36(7): 623-633, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35534690

RESUMO

AIM: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. METHODS: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3-14 days before (pre-ICIT) and 21-28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). RESULTS: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. CONCLUSION: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03426657.


Assuntos
Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço , Linfócitos T CD8-Positivos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imunoterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos
3.
Leukemia ; 31(4): 829-836, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28074067

RESUMO

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86+pDC frequencies than normal donors (P<0.0024), whereas TFR patients had consistently low CD86+pDC (n=12). This suggested that low CD86+pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6-47.9) for patients with >95 CD86+pDC per 105 lymphocytes, but 70.0% (95% CI 59.3-78.3) for patients with <95 CD86+pDC (hazard ratio (HR) 3.4, 95%-CI: 1.9-6.0; P<0.0001). Moreover, only patients with <95 CD86+pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1-0.8; P=0.0263). High CD86+pDC counts significantly correlated with leukemia-specific CD8+ T-cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21-0.92; P=0.0098). Our data demonstrate that CML patients with high CD86+pDC counts have a higher risk of relapse after TKI discontinuation.


Assuntos
Antígeno B7-2/metabolismo , Antígeno CTLA-4/metabolismo , Células Dendríticas/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Adulto , Idoso , Antígeno B7-2/genética , Biomarcadores , Contagem de Células , Células Dendríticas/imunologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Indução de Remissão , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , Adulto Jovem
4.
Leukemia ; 29(5): 1060-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25434303

RESUMO

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Alelos , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Cariotipagem , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo
5.
Bone Marrow Transplant ; 47(4): 574-80, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21927036

RESUMO

The prognosis of patients suffering from respiratory failure (RF) after allogeneic hematopoietic SCT (HSCT) is poor. However, early treatment for using non-invasive ventilation (NIV) may be of benefit. We conducted a randomized trial to prove the impact of early NIV in patients in the early post-transplant period. A total of 526 patients undergoing HSCT in a single center were monitored for signs of RF. Patients with RF were enrolled into either treatment arm A (oxygen supply only) or treatment arm B (oxygen+intermittent NIV). RF had to be diagnosed in 86 patients (16%). RF was an independent risk factor for both short-term (100 day mortality/ OR 2.76; P<0.001) and long-term survival (OR 1.57; P<0.01). Although early RF treatment with NIV was associated with a decreased rate of failure to achieve sufficient oxygenation (39% in arm A vs 24% in arm B, P=0.17), neither intensive care unit admission rate, nor need for intubation or survival parameters were affected by the treatment strategy. An early interventional strategy using NIV was not associated with improvement of the prognosis of the patients. The limited influence of NIV may be related to the study design allowing for switching of treatment in case of unsatisfactory efficacy.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Respiração Artificial , Insuficiência Respiratória/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Intervalo Livre de Doença , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Oxigênio/farmacologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Taxa de Sobrevida , Transplante Homólogo
6.
Leukemia ; 23(4): 656-63, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19151774

RESUMO

Loss of p53 -- a tumor suppressor gene located on the short arm of chromosome 17 (band 17p13.1) -- was detected in 105 out of 2272 (5%) adult acute myeloid leukemia (AML) patients who took part in the Study Alliance Leukemia AML96 and AML2003 multi center trials. There were 85 patients with 17p (p53) deletion with multiple aberrations and 20 patients with a 17p (p53) deletion as single aberration or with only one additional chromosomal abnormality. None of the p53-deleted patients displayed additional low-risk aberrations, like t(8;21) or inv(16). Significant positive association between p53 deletion and other high-risk factors was identified for del(5q) (P<0.001), -5 (P<0.001) and -7 (P<0.05). The molecular risk factors FLT3-ITD and NPM1 mutation showed an inverse correlation to the p53 deletion in complex aberrant patients (P<0.001). The multivariate analysis revealed p53 deletion without multiple aberrations as an independent negative prognostic factor for disease-free survival (P<0.001), relapse risk (P=0.028) and overall survival (P<0.001). Thus, the single p53 deletion should be considered as a high-risk aberration for future risk-adapted treatment strategies in AML.


Assuntos
Cromossomos Humanos Par 17 , Deleção de Genes , Genes p53 , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Nucleofosmina , Prognóstico , Recidiva , Fatores de Risco , Taxa de Sobrevida , Proteína Supressora de Tumor p53 , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genética
7.
Bone Marrow Transplant ; 43(3): 245-51, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18820709

RESUMO

Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They have been used in patients with steroid-refractory acute GVHD (aGVHD), but their relevance as a therapeutic agent targeting aGVHD has still to be defined. In this case series, we report 13 patients with steroid-refractory aGVHD who received BM-derived MSC expanded in platelet lysate-containing medium from unrelated HLA disparate donors. MSC were characterized by their morphological, phenotypical and functional properties. All tested preparations suppressed the proliferation of in vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 x 10(6)/kg (range 0.6-1.1). The median number of MSC applications was 2 (range 1-5). Only two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days, five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment. In our patient cohort, response to MSC transfusion was lower than in the series reported earlier. However, our experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD.


Assuntos
Plaquetas/fisiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Doença Aguda , Adulto , Idoso , Plaquetas/química , Linfócitos T CD4-Positivos/imunologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores/uso terapêutico , Ativação Linfocitária , Masculino , Células-Tronco Mesenquimais/imunologia , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Ann Oncol ; 20(1): 175-81, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18687982

RESUMO

BACKGROUND: Some patients with glioblastoma multiform do not respond to temozolomide even though they have aberrant promoter methylation of the DNA repair enzyme O(6)-methylguanine methyltransferase (MGMT). This suggests that additional factors hamper temozolomide cytotoxicity. We aimed to confirm first that temozolomide is a target for the multidrug resistance transporter MDR1/ABCB1 and second to investigate whether genetic variants of the MDR1 gene are associated with the survival of glioblastoma patients treated with temozolomide. MATERIALS AND METHODS: Temozolomide-mediated cytotoxicity was determined by the colorimetric methyl-thiazol-tetrazolium assay in MDR-expressing and MDR-nonexpressing cell lines. Genotypes of three single nucleotide polymorphisms (SNPs) of the MDR1 gene (C1236T, G2677T, and C3435T), MDR1 mRNA expression levels, and the MGMT promoter methylation status were analyzed in 112 glioblastoma patients who had been treated either by surgery plus radiotherapy alone or by additional temozolomide chemotherapy. RESULTS: In vitro analysis revealed that temozolomide-mediated cytotoxicity is dependent on MDR1 expression. Multivariate analysis of MDR1 genotypes showed that the C/C variant of the exon12 C1236T SNP is predictive for survival of patients treated with temozolomide. This effect was independent of the MGMT methylation status. Patients with the C/C genotype had a 2-year overall survival of 37% compared with 8% and 10% for patients with C/T and T/T genotypes, respectively (P=0.02). No influence was seen in the group of patients with radiotherapy only. CONCLUSION: The genotype of the MDR1 exon12 C1236T SNP is a novel independent predictive factor for outcome of temozolomide treatment in glioblastoma patients.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/diagnóstico , Glioblastoma/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Dacarbazina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Frequência do Gene , Genótipo , Glioblastoma/genética , Glioblastoma/mortalidade , Humanos , Células K562 , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologia , Prognóstico , Temozolomida , Resultado do Tratamento , Adulto Jovem
10.
Int J Hematol ; 88(4): 381-386, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18836794

RESUMO

Neurotoxicity of cytarabine (AraC) is believed to be related to renal insufficiency. We examined the plasma pharmacokinetics of AraC and its deamination product uracil arabinoside (AraU) in four patients with AML and concomitant severe renal insufficiency after treatment with AraC. Additionally, in one of these patients the concentration of intracellular AraCTP, the active metabolite of AraC, was analysed. Patients 2 and 3 were treated with AraC 1.0 g/m(2) infused for 3 h at 12-h intervals on days 1-4. Patient 1 received the same schedule of AraC with 0.5 g/m(2) and patient 4 with 0.25 g/m(2) AraC. Plasma concentrations of AraC, AraU and the intracellular concentration of AraCTP were analysed at different time points using HPLC. AraC pharmacokinetics in patients with severe renal insufficiency was comparable to patients with normal renal function. Peak plasma levels as well as intracellular AraCTP kinetics were also not significantly influenced by renal dysfunction. As expected from the high dose AraC pharmacokinetic parameters, the AraU serum levels accumulated during treatment. Under the conditions of renal impairment, AraU half-life was about 75 h and the AUC was about 12-fold higher than for patients with normal renal function. AraU could be the pathophysiologic cause for the known correlation between the incidence of neurotoxicity and renal insufficiency in high-dose AraC. To avoid AraU accumulation, intermittent hemodialysis during high-dose AraC treatment could be a suitable method considering the low protein-binding and low distribution volume of AraU.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Arabinofuranosiluracila/farmacocinética , Citarabina/efeitos adversos , Citarabina/farmacocinética , Falência Renal Crônica/sangue , Falência Renal Crônica/induzido quimicamente , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Feminino , Meia-Vida , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/sangue
12.
Bone Marrow Transplant ; 42(2): 113-20, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18362900

RESUMO

As low trough levels of mycophenolic acid (MPA) have been measured in recipients of allo-SCTs, we performed a pilot study targeting mycophenolate mofetil (MMF) doses according to the MPA area under the concentration (AUC) levels. Twenty-nine patients were transplanted from matched sibling (n=7) and unrelated donors (n=22). Tacrolimus was given orally from day -1 to achieve trough blood levels of 5-10 ng/ml. MMF was started on day 0 at 1500 mg intravenously b.i.d. AUC measurements of MPA by HPLC were scheduled on days 3, 7 and 11 after transplantation. The MMF dose was modified to achieve an MPA AUC of 35-60 microg/ml/h. With the respective adjustments 66 and 75% surpassed the lower AUC target on days 7 and 11, respectively. The cumulative incidence of grade III-IV acute GVHD was 28% (8/29). Eight out of 24 evaluable patients (33%) suffer from limited (n=3) or extensive (n=5) chronic GVHD. Overall, the results of this study suggest that targeting of MPA exposure is feasible early after transplantation. A simplified MMF targeting strategy based on MPA C(max) or C(2h) levels seems to be warranted in future trials involving more patients at later time points in the outpatient setting.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Adulto , Idoso , Área Sob a Curva , Monitoramento de Medicamentos , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Transplante Homólogo
13.
Cell Prolif ; 40(3): 355-66, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17531080

RESUMO

OBJECTIVES: Recent data show that Imatinib mesylate (IM) also affects haematopoietic stem cells (HSC), T lymphocytes and dendritic cells that do not harbour constitutively active tyrosine kinases. MATERIALS AND METHODS: We evaluated possible effects of IM on human bone marrow-derived mesenchymal stem cells (MSC) in vitro. RESULTS: Screening the activity of 42 receptor tyrosine kinases revealed an exclusive inhibition of platelet-derived growth factor receptorbeta (PDGFRbeta). Analysis of downstream targets of PDGFRbeta demonstrated IM-mediated reduction of Akt and Erk1/2 phosphorylation. Culture of MSC with IM led to the reversible development of perinuclear multi-vesicular bodies. The proliferation and clonogenicity of MSC were significantly reduced compared to control cultures. IM favoured adipogenic differentiation of MSC whereas osteogenesis was suppressed. The functional deficits described led to a 50% reduction in the support of clonogenic haematopoietic stem cells, cultured for 1 month on a monolayer of MSC with IM. CONCLUSION: In summary, inhibition of PDGFRbeta and downstream Akt and Erk signalling by IM has a significant impact on proliferation and differentiation of human MSC in vitro.


Assuntos
Antineoplásicos/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Piperazinas/farmacologia , Pirimidinas/farmacologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Adipócitos/citologia , Benzamidas , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Clonais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Mesilato de Imatinib , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteócitos/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
14.
Bone Marrow Transplant ; 39(4): 201-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17211431

RESUMO

Fludarabine is commonly used in combination with busulfan as part of conditioning regimens before allogeneic stem cell transplantation. So far, no data are available on busulfan-fludarabine drug interactions in transplant recipients. The pharmacokinetic (PK) properties of F-ara-A (9-beta-D-arabinosyl-2-fluoradenine) before and after application of busulfan were prospectively investigated in 16 patients with hematological malignancies. The conditioning regimen consisted of intravenous fludarabine 30 mg/m(2) over 30 min from day -6 to day -3, and oral busulfan given at 1 mg/kg every 6 h from day -5 to day -2. PK parameters of F-ara-A, derived from plasma and urine on day -6, -5, -4 and -3, were determined using high-performance liquid chromatography (HPLC). AUC, C(max), t(1/2), Cl(total) and V(SS) were 21.9 microMh, 3.5 microM, 13.0 h, 4.3 l/h/m(2), 60.0 l/m(2) on day -6 and 22.4 microMh, 3.5 microM, 14.0 h, 4.7 l/h/m(2), 69.0 l/m(2) on day -5 to (-2), respectively. Cl(renal) and the urine-recovery were 4.8 l/h, 43.7% of the fludarabine dose on day -6 and 3.9 l/h, 44.2% of the fludarabine dose on day -5 to (-2), respectively. There were no changes in PK parameters of fludarabine given before and after intake of busulfan. This implies that a clinically relevant busulfan-fludarabine drug interaction is unlikely.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bussulfano/administração & dosagem , Bussulfano/farmacocinética , Interações Medicamentosas , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vidarabina/farmacocinética
18.
Leukemia ; 20(4): 707-14, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16482208

RESUMO

There is substantial need to improve the outcome of patients with high-risk acute myeloid leukemia (AML). The clinical trial reported here investigated a new approach of up-front allogeneic hematopoietic stem cell transplantation (HSCT), provided a median of 40 days (range 22-74) after diagnosis, in twenty-six consecutive patients with newly-diagnosed high-risk AML characterized by poor-risk cytogenetics (n = 19) or inadequate blast clearance by induction chemotherapy (IC, n = 7). The median age was 49 years (range 17-68). During IC-induced aplasia after the 1st (n = 11) or 2nd (n = 15) cycle, patients received allogeneic peripheral blood stem cells (PBSC) from related (n = 11) or unrelated (n = 15) donors following a fludarabine-based reduced-intensity regimen. Seventeen patients were not in remission before HSCT with a median marrow blast count of 34% (range 6-70). All patients achieved rapid engraftment and went into remission with complete myeloid and lymphatic chimerism. Grades II to IV acute GvHD occurred in 14 (56%) and extensive chronic GvHD was documented in 8 (35%) patients. The probability of disease-free survival was 61% with only three patients relapsing 5, 6 and 7 months after transplantation, respectively. Up-front allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in high-risk AML patients and warrants further investigation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimerismo , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento
19.
Bone Marrow Transplant ; 36(12): 1083-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16247435

RESUMO

A total of 22 patients with acute myeloid leukemia (AML) in first complete remission receiving autologous blood stem cell transplantation (ABSCT) were investigated in order to determine factors affecting outcome. All but two patients had a normal karyotype and received the same high-dose chemotherapy followed by G-CSF-mobilized peripheral blood stem cells after the second (n=5) or third (n=17) course of induction and post-remission chemotherapy, respectively. With a median follow-up of 30 months, the median disease-free survival is 24.1 months. Univariate analysis showed that three chemotherapy cycles before ABSCT were associated with a significant better disease-free survival (P=0.0018) and overall survival (P=0.0033), whereas the presence of an FLT3-mutation (n=6) showed no impact. The number of megakaryocytic progenitors (CFU-MK) infused tended to correlate with primary platelet engraftment (P=0.07) and were predictive for neutrophil (P=0.011) and platelet counts (P=0.009) 180 days after transplantation. Patients receiving a higher amount of CFU-MK had a better event-free survival (P=0.02). Our data suggest that the content of CFU-MK within the graft predicts the quality of hematological recovery and long-term disease control. Additionally, a minimum of three chemotherapy cycles before ABSCT seems to be associated with an improved outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Antígenos CD34/biossíntese , Antineoplásicos/farmacologia , Plaquetas , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Cariotipagem , Leucaférese , Masculino , Megacariócitos/citologia , Pessoa de Meia-Idade , Mutação , Indução de Remissão , Células-Tronco/citologia , Fatores de Tempo , Transplante Autólogo/métodos , Resultado do Tratamento
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