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1.
Transplant Cell Ther ; 28(12): 847.e1-847.e8, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36179987

RESUMO

Although autologous hematopoietic cell transplantation (HCT) is an established therapy for patients with relapsed acute promyelocytic leukemia (APL) after returning to complete remission (CR), the role of allogeneic HCT remains unclear for treating relapsed APL. This study aimed to investigate allogeneic HCT outcomes in patients with relapsed APL, focusing particularly on those who underwent transplantation in non-CR and those who had relapsed after prior autologous HCT. We retrospectively analyzed Japanese nationwide transplantation registry data of patients with relapsed APL age ≥16 years who underwent allogeneic HCT between 2006 and 2020. A total of 195 patients were eligible for this analysis, including 69 who underwent transplantation in non-CR and 55 who relapsed after prior autologous HCT. The median duration of follow-up for survivors was 5.4 years. Multivariate analysis revealed that both non-CR at transplantation (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12 to 2.71; P = .014) and prior autologous HCT (HR, 2.10; 95% CI, 1.28 to 3.44; P = .013) were associated with higher risks of overall mortality. The 5-year overall survival (OS) rates for patients who underwent transplantation in CR and non-CR were 58% and 39%, respectively (P = .085), if they did not have a history of prior autologous HCT. In the patients who had relapsed after prior autologous HCT, the 5-year OS rate was 47% for those who underwent allogeneic HCT in CR and 6% for those who did so in non-CR (P = .001). Allogeneic HCT still provides an opportunity for long-term survival for certain patients with relapsed APL for whom autologous HCT is unlikely to be effective. The dismal outcome of those with prior autologous HCT who underwent allogeneic HCT in non-CR poses a significant therapeutic challenge.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Promielocítica Aguda , Humanos , Adolescente , Leucemia Promielocítica Aguda/cirurgia , Transplante Homólogo , Estudos Retrospectivos , Transplante Autólogo
2.
Ann Hematol ; 93(6): 941-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24408159

RESUMO

Arsenic trioxide (ATO) is an effective therapy for relapsed acute promyelocytic leukemia (APL) patients; however, the optimal treatment strategy remains unclear, and knowledge of the prognostic factors is still limited. We retrospectively analyzed the outcomes of 64 consecutive first relapsed APL patients (12 with molecular relapse and 52 with hematologic relapse). Patients received re-induction with intravenous ATO-based regimens. Patients who achieved a CR2 were offered further courses of alternating ATO/conventional chemotherapy with or without stem cell transplantation (SCT). With a median follow-up of 27 months (range, 6-57) in the molecular relapsed subgroup, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 81.5 % and 100 %, respectively. With a median follow-up of 38 months (range, 0-129) in the hematologic relapse group, the 3-year RFS and OS rates were 57.1 % and 72.1 %, respectively. Furthermore, in the hematologic relapse group, we compared the outcome between relapsed patients after previous ATO therapy (n = 20) with those who did not receive prior ATO therapy (n = 32). The CR2 rate was 80 % (16/20) vs. 93.8 % (30/32), (p = 0.189). However, the relapse rate was 68.8 % (11/16) vs. 33.3 % (10/30), (p = 0.03). The 4-year OS rate was 62.4 % vs. 71.2 %, (p = 0.816), and the 4-year RFS rate was 29.8 % vs. 66.2 % (p = 0.023). The results indicate that, irrespective of frontline therapy with ATO, salvage therapy with an ATO-based regimen remains effective. However, the long-term survival for those patients who received previous ATO-based treatment was inferior compared to those who did not receive prior ATO. In addition, the alternating ATO/chemotherapy strategy can be a post-remission treatment option in a subset of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Trióxido de Arsênio , Arsenicais/administração & dosagem , Terapia Combinada , Avaliação de Medicamentos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Leucemia Promielocítica Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Óxidos/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
Cancer Sci ; 104(10): 1339-45, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23837667

RESUMO

For patients with relapsed acute promyelocytic leukemia (APL), all-trans retinoic acid-based salvage regimens can achieve second complete remission (CR2), but the optimal post-remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)-HSCT, 21 received allogeneic (allo)-HSCT, and 30 received various regimens other than HSCT. The 5-year event-free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non-HSCT group, 41.7%, 83.3% and 58.3% in the auto-HSCT group and 71.1%, 76.2% and 9.8% in the allo-HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo-HSCT group than in other groups. Allo-HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation-related mortality (19%). Among older patients (age ≥40 years), the 5-year OS was significantly better in the non-HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Promielocítica Aguda/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Trióxido de Arsênio , Arsenicais/uso terapêutico , Benzoatos/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Óxidos/uso terapêutico , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Tetra-Hidronaftalenos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/estatística & dados numéricos , Transplante Homólogo/estatística & dados numéricos , Resultado do Tratamento , Tretinoína/uso terapêutico , Adulto Jovem
4.
Clin Lymphoma Myeloma Leuk ; 13(4): 485-92, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23769669

RESUMO

BACKGROUND: Outcomes in patients with acute promyelocytic leukemia (APL) have improved; however, a significant number of patients still relapse despite receiving all-trans-retinoic acid (ATRA) and arsenic-based therapies. PATIENTS AND METHODS: Outcomes of patients with relapsed APL who were treated at our institution (1980-2010) and who received HCT were compared with those who received chemotherapy (CT) only. RESULTS: Among 40 patients, 24 received HCT (autologous [auto] HCT, 7; allogeneic [allo] HCT, 14; both, 3); 16 received CT only. The median age at diagnosis was 36 years (range, 13-50 years), 31 years (range, 16-58 years), and 44 years (range, 24-79 years) for the auto-HCT, allo-HCT, and CT groups, respectively. Ten (100%) patients who received auto-HCT and 12 (71%) who received allo-HCT were in complete remission at the time of the HCT. The median follow-ups in the auto-HCT, allo-HCT, and CT groups were 74 months (range, 26-135 months), 118 months (range, 28-284 months), and 122 months (range, 32-216 months), respectively. Transplantation-related mortality (1 year) after auto-HCT and allo-HCT were 10% and 29%, respectively. The 7-year event-free survival after auto-HCT and allo-HCT was 68.6% and 40.6%, respectively (P = .45). The 7-year overall survival was 85.7%, 49.4%, and 40% in the auto-HCT, allo-HCT, and CT groups, respectively (P = .48). CONCLUSION: Both auto-HCT and allo-HCT are associated with durable remission and prolonged survival. All 3 strategies (auto-HCT, allo-HCT, CT) were found to be feasible in the relapsed APL setting and result in long-term disease control in selected patients. In this retrospective analysis, overall survival for patients who received HCT was not significantly better than patients who received CT only, but a trend toward better outcomes was seen in patients who underwent auto-HCT, although not statistically significant.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Recidiva , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
5.
Blood ; 121(16): 3095-102, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23412094

RESUMO

The optimal treatments for relapsed acute promyelocytic leukemia (APL) remain equivocal. We conducted a phase 2 study to evaluate the efficacy and feasibility of a sequential treatment consisting of induction and consolidation with arsenic trioxide (ATO), peripheral blood stem cell (PBSC) harvest after high-dose cytarabine chemotherapy, and autologous hematopoietic cell transplantation (HCT). Between 2005 and 2009, 35 patients (26 with hematologic and 9 with molecular relapse) were enrolled. Induction therapy resulted in complete remission in 81% of those with hematologic relapse, and most patients became negative for PML-RARα after the first ATO consolidation course, but 4 remained positive. Administration of the second ATO consolidation course further decreased the transcript levels in 3 patients. In total, 25 patients proceeded to PBSC harvest, all of whom successfully achieved the target CD34+ cell doses, and 23 underwent autologous HCT with PML-RARα-negative PBSC graft. Posttransplant relapse occurred in 3 patients, and there was no transplant-related mortality. With a median follow-up of 4.9 years, the 5-year event-free and overall survival rates were 65% and 77%, respectively. These findings demonstrate the outstanding efficacy and feasibility of the sequential treatment featuring ATO and autologous HCT for relapsed APL. This study was registered at http://www.umin.ac.jp/ctr/ as #C000000302.


Assuntos
Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Óxidos/uso terapêutico , Adulto , Trióxido de Arsênio , Citarabina/uso terapêutico , Feminino , Seguimentos , Humanos , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Proteínas de Fusão Oncogênica/genética , Indução de Remissão , Transcrição Gênica , Transplante Autólogo , Adulto Jovem
6.
Cancer Sci ; 102(11): 1929-37, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21790894

RESUMO

Acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia (AML), results from the arrest of the maturation of hematopoietic progenitors at the promyelocyte stage. It has been shown that APL is associated with a reciprocal chromosomal translocation, involving chromosomes 15 and 17, which fuses the gene encoding the retinoic acid receptor α (RARα) and the promyelocytic leukemia (PML) gene. The resultant PML-RARα fusion protein plays a critical role in the pathogenesis of APL. Although there are many subtypes of AML, all are typically managed using a standard chemotherapy regimen of an anthracycline plus cytarabine arabinoside (CA). Despite high rates of complete remission following standard chemotherapy, most patients relapse and long-term disease-free survival is only 30-40%. The introduction of drugs such as all-trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML-RARα fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. The purposes of the present review are to provide the latest results and future directions of clinical research into APL and to illustrate how new therapies, such as ATRA plus anthracycline-based induction and consolidation therapy, risk-adapted therapy, salvage therapy containing arsenic trioxide-based regimens, and hematopoietic stem cell transplantation, have improved the treatment outcomes for APL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação/tendências , Quimioterapia de Indução/tendências , Leucemia Promielocítica Aguda/tratamento farmacológico , Quimioterapia de Manutenção/tendências , Antraciclinas/administração & dosagem , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/farmacologia , Diferenciação Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Citarabina/administração & dosagem , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/cirurgia , Estudos Multicêntricos como Assunto , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas de Fusão Oncogênica/fisiologia , Óxidos/administração & dosagem , Óxidos/farmacologia , Risco , Terapia de Salvação , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Tretinoína/farmacologia
7.
J Clin Oncol ; 29(18): e534-6, 2011 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21482998

Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzoatos/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Terapia de Salvação , Tetra-Hidronaftalenos/uso terapêutico , Adulto , Aminoglicosídeos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Trióxido de Arsênio , Arsenicais/administração & dosagem , Benzoatos/administração & dosagem , Medula Óssea/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Terapia Combinada , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Gemtuzumab , Transplante de Células-Tronco Hematopoéticas , Humanos , Idarubicina/administração & dosagem , Leucemia Promielocítica Aguda/cirurgia , Infiltração Leucêmica/tratamento farmacológico , Infiltração Leucêmica/patologia , Masculino , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Óxidos/administração & dosagem , Cintilografia , Indução de Remissão , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/tratamento farmacológico , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/secundário , Tetra-Hidronaftalenos/administração & dosagem , Tretinoína/administração & dosagem
10.
Ter Arkh ; 82(7): 20-5, 2010.
Artigo em Russo | MEDLINE | ID: mdl-20853604

RESUMO

AIM: To analyze the specific features of recurrences of acute promyelocytic leukemia (APL) in children after standard therapy with daunorubicin, cytosine arabinoside (Ara-C), all-trans retinoic acid (ATRA) and to develop further programmed treatment policy. SUBJECTS AND METHODS: The study included 9 patients with recurrent APL. The recurrences developed significantly more frequently in a very high-risk group (patients with minimal residual disease being preserved after the intensive therapy phase). Induction used arsenic trioxide (ATO) and/or standard chemotherapy + ATRA; ATO monotherapy was in consolidation. CD34+ cells were mobilized until molecular remission was achieved with high-dose Ara-C and granulocyte colony-stimulating factor. Pretransplantation conditioning involved melfalan as a basic drug in combination with high-dose AraC (5 pts), treosulfan (1 pt) or bisulfan (1 pt). Six patients received gemtusumab ozogamicin, 3-9 mg/m2, at different stages of therapy. RESULTS: Before therapy one patient died; 8 patients achieved the second molecular remission; CD34+ cell mobilization and sampling were effective in 7 cases. Five patients were in long-term molecular remission after autologous hemopoietic stem cell transplantation (autoHSCT). Follow-up was 23-40 months. One patient is being prepared for transplantation. Following autoHSCT, another patient with a developed repeat recurrence died from complications due to related partially compatible transplantation. Visceral, including cardiological, toxicity of therapy was insignificant. In the APL-2003 protocol, overall and event-free survival rates were 93 +/- 3 and 76 +/- 6%, respectively. CONCLUSION; The application of ATO and autoHSCT in recurrent APL makes it possible to achieve and preserve the second molecular remission in case of insignificant extrahematological toxicity. Russian clinics should have access to ATO.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Promielocítica Aguda/prevenção & controle , Condicionamento Pré-Transplante/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Humanos , Lactente , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Leucemia Promielocítica Aguda/cirurgia , Óxidos/administração & dosagem , Óxidos/uso terapêutico , Indução de Remissão , Prevenção Secundária , Transplante Autólogo
11.
Dermatol Online J ; 15(9): 4, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19930991

RESUMO

A major complication following hematopoietic stem cell transplantation is graft versus host disease. Cutaneous manifestations of chronic graft versus host disease (cGVHD) are varied and this condition impacts patient outcomes and quality of life. We describe two cases of lichen sclerosus et atrophicus-like cGVHD developing in patients after hematopoietic stem cell transplantation. Both patients presented clinically with patches of pigmentary changes and scaling that displayed classic histologic features of lichen sclerosus et atrophicus. The skin is a frequent target organ of cGVHD and often the presenting location of the disease, making dermatologists key in recognition and management. It has been proposed that cutaneous cGVHD is a spectrum of disease and the lesions may evolve through various stages. Lichen sclerosus et atrophicus-like cGVHD may represent a phase in this continuum or a distinct sub-type of disease. Remaining cognizant of the potential manifestations of disease is key for prompt recognition and proper treatment.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Líquen Escleroso e Atrófico/diagnóstico , Clobetasol/uso terapêutico , Terapia Combinada , Diagnóstico Diferencial , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/patologia , Humanos , Hidrocortisona/uso terapêutico , Imunossupressores/uso terapêutico , Leucemia Promielocítica Aguda/radioterapia , Leucemia Promielocítica Aguda/cirurgia , Transfusão de Linfócitos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fotoferese , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Tacrolimo/uso terapêutico , Triancinolona/uso terapêutico
12.
Biol Blood Marrow Transplant ; 15(11): 1479-84, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19822309

RESUMO

In patients with relapsed acute promyelocytic leukemia (APL), the best consolidation regimen following induction of remission with arsenic trioxide (ATO) remains to be defined. Since January 2000, 37 patients with relapsed APL were treated at our center. The median age was 34 years (range, 6-57 years), and there were 20 males (54.1%). The median duration of first remission was 20.3 months (range, 2.9-81.2 months). Relapse was treated with single-agent ATO in 22 patients (59.5%), ATO+ATRA in 5 patients (13.5%), and ATO+ATRA + anthracycline in 10 patients (27%). Thirty-three patients (89%) achieved molecular remission after induction and a consolidation course. Fourteen patients opted to undergo autologous stem cell transplantation (SCT), and the remaining 19 patients received monthly cycles of ATO as a single agent (n=13) or ATO+ATRA (n=6) for 6 months. At a median follow-up of 32 months, the 5-year Kaplan-Meier estimate of event-free survival (EFS) was 83.33% +/- 15.21% in those who underwent autologous SCT versus 34.45% +/- 11.24% in those who did not (P=.001; log-rank test). Following remission induction with ATO-based regimens in patients with relapsed APL, consolidation with autologous SCT is associated with a significantly superior clinical outcome compared with ATO- and ATO+ATRA-based maintenance regimens.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Terapia de Salvação/métodos , Adolescente , Adulto , Antraciclinas/administração & dosagem , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/uso terapêutico , Biomarcadores Tumorais/sangue , Criança , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/mortalidade , Leucemia Promielocítica Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Proteínas de Fusão Oncogênica/sangue , Óxidos/administração & dosagem , Óxidos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Recidiva , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento , Tretinoína/administração & dosagem , Adulto Jovem
13.
Pediatr Blood Cancer ; 51(4): 521-4, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18493994

RESUMO

BACKGROUND: Relapsed acute promyleocytic leukemia (APL) is treated with re-induction chemotherapy, commonly arsenic trioxide, and stem cell transplantation (SCT). The effect of arsenic trioxide on autologous peripheral blood stem cell collection is unknown. PROCEDURE: Five pediatric patients with relapsed APL had PML-RARA negative peripheral blood stem cells mobilized (four after arsenic trioxide) and underwent autologous SCT after cyclophosphamide (60 mg/kg x 2) and total body irradiation (TBI-fractionated 1,200 cGy) conditioning. RESULTS: All five patients remain in molecular remission a median of 20 months post-transplant. CONCLUSION: Autologous SCT performed during molecular remission is a treatment option for pediatric patients with relapsed APL and may provide durable leukemia-free survival without the complications of allogeneic transplantation.


Assuntos
Células-Tronco Hematopoéticas/metabolismo , Leucemia Promielocítica Aguda/cirurgia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Criança , Pré-Escolar , Sobrevivência de Enxerto , Humanos , Leucemia Promielocítica Aguda/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Recidiva , Terapia de Salvação , Transplante Autólogo/efeitos adversos
15.
Bone Marrow Transplant ; 40(8): 773-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17700597

RESUMO

Secondary failure of platelet recovery (SFPR), which is a delayed decline in platelet count after primary recovery following myeloablative hematopoietic SCT, is a significant problem in allogeneic SCT. However, its clinical characteristics have not been well described in autologous SCT for acute myeloid leukemia. We reviewed 11 consecutive patients who had received autologous or syngeneic SCT for acute promyelocytic leukemia. Seven of 11 patients (64%) had SFPR, which is defined as a decline in the platelet count to less than 30,000/microl for more than 7 days. The median onset of SFPR was day 36 (range, 25-51 days) and the median duration of thrombocytopenia was 13 days (range, 4-25 days). Of nine patients who received busulfan-containing preparative regimens, seven (78%) had SFPR and one had delayed primary platelet count recovery. Neither patient who received cyclophosphamide and total body irradiation as preparative regimens had SFPR. The clinical courses of SFPR were transient and self-limited. SFPR was not associated with relapse of underlying diseases, graft failure or other fatal morbidities. The unexpectedly high prevalence and the characteristics of SFPR may provide additional information on management following autologous SCT for acute myeloid leukemia.


Assuntos
Leucemia Promielocítica Aguda/cirurgia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Trombocitopenia/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Transplante Autólogo , Transplante Isogênico
16.
Br J Haematol ; 137(3): 248-51, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17408466

RESUMO

Graft failure (GF) can be a fatal complication following haematopoietic stem cell transplantation (HSCT). We report four patients who developed early GF after unrelated HSCT and who subsequently received a double unrelated cord blood transplant (dUCBT) after reduced-intensity conditioning, at a median 15 d after the decision to perform a second transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimaerism of one unit. Acute GVHD grades II-IV was observed in three patients. Three are alive, between 12 and 25 months after dUCBT. In conclusion, dUCBT is a promising procedure to treat early GF.


Assuntos
Rejeição de Enxerto/cirurgia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/cirurgia , Doença Aguda , Adolescente , Adulto , Anemia Aplástica/cirurgia , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Evolução Fatal , Feminino , Sangue Fetal , Doença Enxerto-Hospedeiro , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Promielocítica Aguda/cirurgia , Masculino , Reoperação , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos
17.
Leukemia ; 21(3): 446-52, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17205057

RESUMO

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age

Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Criança , Pré-Escolar , Terapia Combinada , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Idarubicina/administração & dosagem , Estimativa de Kaplan-Meier , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/mortalidade , Leucemia Promielocítica Aguda/patologia , Leucemia Promielocítica Aguda/cirurgia , Lipossomos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Neoplasia Residual , Proteínas de Fusão Oncogênica/sangue , Prognóstico , Recidiva , Indução de Remissão , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Tretinoína/administração & dosagem
19.
Haematologica ; 90(9): 1231-5, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16154847

RESUMO

Recent studies have demonstrated the beneficial effects of arsenic trioxide (ATO) in the treatment of relapsed acute promyelocytic leukemia (APL). The aim of this review is to discuss the role of ATO in the management of APL. Based on the available clinical evidence, a tentative algorithm is proposed for the treatment of patients who relapse after or are refractory to all trans-retinoic acid-based therapy. Other opportunities for the use of ATO in front-line treatment of APL are also discussed, especially its potential use in patients at high risk of relapse and in those with contraindications to chemotherapy or in whom the amount of chemotherapy should be reduced.


Assuntos
Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos/uso terapêutico , Trióxido de Arsênio , Humanos , Leucemia Promielocítica Aguda/cirurgia
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