RESUMEN
Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of â¼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.
Asunto(s)
Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Neoplasias Primarias Secundarias/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/inducido químicamente , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib/uso terapéutico , Incidencia , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Linfoma no Hodgkin/inducido químicamente , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Factores SexualesRESUMEN
Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Familia , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Riesgo , Análisis de Supervivencia , Donantes de Tejidos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Treatment options for adults with primary refractory acute myeloid leukaemia (PREF AML) are extremely limited. Although sibling allogeneic stem cell transplantation can result in long-term survival, most patients lack a matched family donor and are destined to die of refractory disease. Greater availability of unrelated donors and improvements in supportive care have increased the proportion of patients with PREF AML in whom allografting is technically feasible, but the outcome of unrelated donor transplantation in this population has not been studied. We therefore analysed overall survival in 168 patients with PREF AML, who underwent unrelated donor transplantation between 1994 and 2006. The 5-year overall survival for the whole group was 22%. In multivariate analysis, fewer than three courses of induction chemotherapy, a lower percentage of bone marrow blasts at transplant and patient cytomegalovirus seropositivity were associated with improved survival. This allowed the development of a scoring system that identified four groups with survival rates between 44±11% and 0%. This study demonstrates an important role for unrelated donor transplantation in the management of selected patients with PREF AML and confirms the importance of initiating an urgent unrelated donor search in patients with no matched sibling donor, who fail to respond to induction chemotherapy.
Asunto(s)
Leucemia Mieloide Aguda/terapia , Donadores Vivos , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Resistencia a Antineoplásicos , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Terapia Recuperativa , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
A haematopoietic SCT (HSCT) can cause severe side effects, which may have a profound impact on a patient's life both physically and psychologically. Some studies have shown that physical activity has positive effects for inpatients after an HSCT. Therefore, the question arises whether a controlled exercise programme right from the beginning of the conditioning phase could help contribute to a patient's physical and psychological recovery. To evaluate the different effects of specific, moderate physical activities on the physical and psychological condition of HSCT patients we performed a controlled randomized study with 64 inpatients undergoing an allogeneic or autologous HSCT. The patients were randomly assigned to two groups. Although the training group took part in a specific programme of exercise therapy twice a day throughout the entire hospitalization phase, patients in the control group were offered the hospital's standard mobilization programme. The results of this study showed significant differences in favour of the training group regarding strength, endurance, lung function and quality of life. However, further studies are needed to confirm these results.
Asunto(s)
Terapia por Ejercicio/métodos , Tolerancia al Ejercicio , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/psicología , Humanos , Pulmón/fisiología , Masculino , Persona de Mediana Edad , Calidad de Vida , Fenómenos Fisiológicos RespiratoriosRESUMEN
Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML). In this study, outcome of 593 patients with MDS/sAML after autologous and allogeneic HCT from a matched unrelated donor (MUD) were compared. A total of 167 (28%) patients received HCT from MUD without prior chemotherapy (MUD-U). The rest received HCT in first complete remission (CR1) (Autologous (Auto-CR1), n=290 (49%), HCT from MUD (MUD-CR1), n=136 (23%)). Survival at 3 years was best in MUD-CR1 (50%) compared to Auto-CR1 (41%) and MUD-U (40%) (P=0.01). Similarly, disease-free survival was 44% for MUD-CR1 compared to Auto-CR1 (28%) and MUD-U (34%) (P=0.03). Treatment-related mortality was 17% in Auto-CR1 compared to MUD-CR1 (38%) and MUD-U (49%) (P<0.001). Relapse for Auto-CR1 was 62% compared to 24 and 30% for MUD-CR1 and MUD-U, respectively (P<0.001). Outcome was best for patients with low tumor burden transplanted 6-12 months after diagnosis. Factors influencing outcome at 3 years were mainly significant in the first 6 months. Only, relapse after autologous HCT remained constant over time. Outcomes after allogeneic HCT in patients of 20-40 and >40 years were similar. Autologous and Allogeneic HCT from MUD offer the possibility of long-term survival to patients with MDS/sAML.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia Mieloide/mortalidad , Leucemia Mieloide/terapia , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Enfermedad Aguda , Adolescente , Adulto , Distribución por Edad , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Donantes de Tejidos , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
In recent years, reduced-intensity conditioning (RIC) regimens before allogeneic stem cell transplantation (SCT) are increasingly used in patients not eligible for conventional conditioning. We did a retrospective, multicenter analysis to assess the feasibility of conditioning with fludarabine and treosulfan before allogeneic SCT in multiple myeloma patients. Thirty-four patients with a median age of 51.5 years were included in the analysis. All patients underwent myeloablation after conditioning followed by stable engraftment, and 29 of 31 evaluable patients (94%) showed early complete hematopoietic chimerism. Non-hematological toxicities were limited and encompassed mainly fever in neutropenia and infections. Grade II-IV acute and chronic graft-versus-host disease was observed in 33 and 39%, respectively. With a median follow-up of 708 days (range 60-1729 days), the median progression-free survival was 180 days. The treatment-related mortality was 10% on day 100 and 25% after 1 year. The median overall survival has not yet been reached. Our data indicate that conditioning with fludarabine and treosulfan before allogeneic SCT is feasible in intensively pretreated multiple myeloma patients and leads to stable engraftment and complete hematopoietic chimerism. Randomized trials are warranted to determine if this approach might be incorporated in an algorithm of multiple myeloma treatment.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos/uso terapéutico , Busulfano/análogos & derivados , Mieloma Múltiple/terapia , Trasplante de Células Madre/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Vidarabina/análogos & derivados , Adulto , Anciano , Busulfano/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vidarabina/uso terapéuticoRESUMEN
Allogeneic stem cell transplantation (SCT) is best performed with an HLA-identical sibling donor (matched related donor, MRD) to reduce the risk of early complications such as acute graft-vs.-host disease (aGvHD). However, as only about 30% of recipients have an MRD for this potentially curative approach, the use of family donors with one or two mismatches in the HLA-antigens (mismatch related donor, MMRD) or fully matched unrelated donors (MUD) (''alternative donors'') has been introduced in the allogeneic SCT setting in recent years. To evaluate the feasibility of allogeneic SCT from alternative donors by using peripheral blood stem cells (PBSC) we initiated a prospective, phase II study in 1996. From April 1996 to July 1998, 18 patients with various hematological malignancies underwent allogeneic SCT from alternative donors (two patients with MUD and 16 patients with MMRD). All patients received stable engraftment and none of the patients had graft rejection. The rate of aGvHD (grades II-IV) and the relapse rate at last follow-up (seven to nine yr after SCT) were with 40% and 24%, respectively, comparable with those found in patients receiving allogeneic SCT from MRD. However, five yr after allogeneic SCT only 17% were alive, which was mainly due to the treatment-related mortality (TRM) rate of 59%. We conclude that allogeneic PBSC transplantation by using alternative donors is associated with an unsatisfying long-term TRM rate. The significance of TRM and particular late deaths has to be evaluated further in this transplantation setting.
Asunto(s)
Leucemia/terapia , Trasplante de Células Madre , Donantes de Tejidos , Antígenos CD/sangre , Familia , Femenino , Filgrastim , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Prueba de Histocompatibilidad , Humanos , Leucemia/mortalidad , Masculino , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Proteínas Recombinantes , Análisis de Supervivencia , Factores de Tiempo , Trasplante HomólogoAsunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/patología , Neoplasias Peritoneales/patología , Ascitis , Células de la Médula Ósea , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Persona de Mediana Edad , Recurrencia , Quimera por Trasplante , Trasplante HomólogoRESUMEN
Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10(-4), respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Anciano , Causas de Muerte , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Hermanos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del TratamientoAsunto(s)
Trasplante de Médula Ósea/efectos adversos , Prueba de Histocompatibilidad , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Síndromes Mielodisplásicos/etiología , Trasplante de Células Madre/efectos adversos , Adulto , Femenino , Humanos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/inmunologíaRESUMEN
A total of 155 patients with acute myeloid leukemia (AML) received hematopoietic stem cell transplants from unrelated donors after standard conditioning. Clinical outcome after the use of two different antithymocyte globulins for the prevention of graft-versus-host disease (GvHD) was analyzed in a retrospective study as follows: rabbit ATG (Thymoglobulin Sangstat/Genzyme, n=49, median age 42 years, 53% in CR, further ATG-S); rabbit ATG (ATG-Fresenius, n=38, median age 42 years, 58% in CR, further ATG-F) or no ATG (n=68, median age 36 years, 55% in CR). The groups were comparable regarding disease status at transplant, age, CMV status and cytogenetics. Grade III-IV acute GvHD was found in 15% in the ATG and 27% in the no ATG group (P=0.44). The most important independent risk factors for chronic GvHD (cGvHD) were the use of ATG, disease status at transplant and conditioning. cGvHD developed significantly more frequently in no ATG group. With the median follow-up of 34 months, the 5-year survival is 42% for those transplanted in CR. To conclude, these data demonstrate that the transplants performed in CR, with ATG, are associated with a good outcome, low incidence of cGvHD and no increase of relapse.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Suero Antilinfocítico/efectos adversos , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Estudios RetrospectivosRESUMEN
We describe successful treatment of a 38-year-old patient with composite lymphoma stage IV(A), who presented with multifocal enlarged lymph nodes. The lymph node histology showed classic morphologic features of Hodgkin's disease, mixed cellularity subtype and follicular B-cell lymphoma. Immunophenotypic analysis showed immunoreactivity for CD20, CD10 and Ki-67 in the malignant small cell population. The areas of Hodgkin's disease demonstrated positive immunoreactivity for CD30 and CD20 in the Hodgkin's cells. Both cell populations were bcl2-oncoprotein positive. Eight courses of dose-escalated BEACOPP were administered. Restaging after chemotherapy showed radiological partial remission, but biopsy confirmed persisting follicular B-cell lymphoma without bone marrow infiltration and no evidence of Hodgkin's disease. He was treated with monoclonal CD 20-antibody (Rituximab) 10 mg/kg weekly for eight consecutive weeks due to marked positivity of CD 20-antigen in follicular lymphoma cells. This treatment was well tolerated and final staging showed complete remission of the composite lymphoma. This patient continues to be in remission 28 months after the end of the treatment. In conclusion, in the very rare case of composite lymphoma a combination of chemotherapy and subsequent immunotherapy might be considered as a promising therapeutic option.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20 , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Antígeno Ki-67 , Leucemia Linfoide/tratamiento farmacológico , Leucemia Linfoide/patología , Linfoma/patología , Masculino , Neprilisina , Inducción de Remisión/métodos , RituximabRESUMEN
Treosulphan has recently demonstrated antileukaemic activity and potent haematopoietic stem cell toxicity. Dose-escalated treosulphan (3 x 12 or 3 x 14 g/m2) combined with cyclophosphamide (Cy) was chosen for a new preparative regimen before allogeneic haematopoietic stem cell transplantation in 18 patients (median age 44, range 19-64 years) with haematological malignancies, considered ineligible for other myeloablative preparative regimens. Pharmacokinetic studies demonstrated rapid treosulphan plasma clearance and a dose-dependent increase of its maximum plasma concentrations and area under the concentration-time curves. Rapid and sustained white blood cell and platelet recovery and full donor chimerism was attained in all evaluable patients. Nonhaematological regimen-related CTC grades 3-4 adverse events were transient and predominantly consisted of cardiac (28%), gastrointestinal (39%), and hepatic (39%) toxicities. The 1-year nonrelapse mortality was 22%. Principal causes of transplant-related lethal events were infections in three of four affected patients. Only one patient died from regimen-related cardiac toxicity. The 1-year relapse estimate is 22%, overall and progression-free survival estimates are 67 and 56%, respectively. In conclusion, this new treosulphan and Cy combination is an effective, comparatively well-tolerated myeloablative preparative regimen even in patients with an increased risk for regimen-related toxic complications.
Asunto(s)
Busulfano/análogos & derivados , Busulfano/administración & dosificación , Ciclofosfamida/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Busulfano/farmacocinética , Busulfano/toxicidad , Causas de Muerte , Relación Dosis-Respuesta a Droga , Femenino , Supervivencia de Injerto , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Farmacocinética , Recurrencia , Medición de Riesgo , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/mortalidad , Trasplante HomólogoRESUMEN
It is unknown whether the addition of antithymocyte globulin (ATG) to reduced-intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in HLA-identical sibling transplantation. Therefore, we analyzed retrospectively data on 83 patients, who received peripheral blood stem cells from HLA-identical siblings after conditioning with either 8 mg/kg BU and 150 mg/m2 FLU (n=45) or 8 mg/kg BU, 180 mg/m2 FLU and 40 mg/kg ATG (n=38). Graft-versus-host disease (GVHD) prophylaxis consisted of CSA alone (n=32) or a combination with either MTX or MMF (n=51). The median age was 52 years. Graft failure occurred in two patients after BU/FLU and in three after BU/FLU/ATG (P=0.66). After conditioning with BU/FLU, platelet recovery was significantly faster (P=0.017), and less platelet (P<0.001) and red blood cell (P=0.002) support was needed. Incidences of acute GVHD grades II and IV were 46 and 49%, respectively. Limited chronic GVHD occurred more often after BU/FLU compared to BU/FLU/ATG (54 vs 23%, P=0.02). The overall survival, non-relapse and relapse mortality did not differ significantly. We conclude that in peripheral blood stem cell transplantation from HLA-identical siblings after reduced-intensity conditioning with BU and FLU, ATG has no major impact on the rate of graft rejection and acute GVHD, but it reduces the incidence of limited chronic GVHD.
Asunto(s)
Suero Antilinfocítico/administración & dosificación , Busulfano/administración & dosificación , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/administración & dosificación , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Vidarabina/administración & dosificación , Enfermedad Aguda , Adulto , Anciano , Enfermedad Crónica , Terapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/mortalidad , Hematopoyesis , Prueba de Histocompatibilidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Hermanos , Análisis de Supervivencia , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.
Asunto(s)
Suero Antilinfocítico/farmacología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Adolescente , Adulto , Niño , Enfermedad Crónica , Femenino , Humanos , Inmunofenotipificación , Inmunosupresores/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Estudios Retrospectivos , Factores de TiempoRESUMEN
PURPOSE: To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15). Minimal residual disease (MRD) was monitored with a clone-specific polymerase chain reaction. RESULTS: After a median follow-up of 2 years, 23 patients are alive (to date). Neutrophil and platelet engraftment occurred after a median of 17.5 and 15 days, respectively. Acute graft-versus-host disease (GVHD) grade 2 to 4 was observed in 17 patients (56%), and chronic GVHD was observed in 21 patients (75%). Twelve patients (40%) achieved a complete remission (CR), and 16 patients (53%) achieved a partial remission. Late CR occurred up to 2 years after transplantation. MRD was monitored in eight patients with CR. All patients achieved a molecular CR. At last follow-up, six patients were in ongoing molecular CR. Causes of death were treatment-related complications in four patients and progressive disease in three patients. The probability of overall survival, progression-free survival, and nonrelapse mortality at 2 years was 72% (95% confidence interval [CI], 54% to 90%), 67% (95% CI, 49% to 85%), and 15% (95% CI, 1% to 29%), respectively. CONCLUSION: Treatment-related mortality after reduced-intensity conditioning followed by allogeneic HSCT was low. The procedure induced molecular remissions in patients with advanced CLL. The observation of late remissions provided evidence of a graft-versus-leukemia effect.
Asunto(s)
Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Linfocítica Crónica de Células B/terapia , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Adulto , Anciano , Niño , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Tasa de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (PAsunto(s)
Trasplante de Células Madre Hematopoyéticas
, Leucemia Mieloide Aguda/terapia
, Acondicionamiento Pretrasplante/métodos
, Adolescente
, Adulto
, Anciano
, Femenino
, Alemania/epidemiología
, Supervivencia de Injerto
, Enfermedad Injerto contra Huésped/etiología
, Trasplante de Células Madre Hematopoyéticas/efectos adversos
, Humanos
, Leucemia Mieloide Aguda/mortalidad
, Leucemia Mieloide Aguda/patología
, Masculino
, Persona de Mediana Edad
, Pronóstico
, Estudios Retrospectivos
, Tasa de Supervivencia
, Acondicionamiento Pretrasplante/efectos adversos
, Trasplante Homólogo
RESUMEN
We report a 30-year-old patient with therapy-refractory T-ALL undergoing unrelated allogeneic PBSCT. He developed severe tumor lysis syndrome (TLS) with extreme biochemical changes, cardiac and neurological symptoms and dialysis-dependent acute renal failure after TBI (4 Gy) on the first day of reduced intensity conditioning (RIC) for unrelated allogeneic PBSCT. The patient's clinical condition was stabilized after beginning daily hemodialysis and treatment for disturbed electrolytes, metabolic acidosis and plasma coagulation, as well as reduction of uric acid by rasburicase. The conditioning therapy and the allogenic PBSCT were scheduled according to the preparative regimen. According to our knowledge, severe TLS induced by 4 Gy TBI has not been reported so far. Regimen-related toxicity using RIC regimen was mild, allowing 30-50% of the patients to have an entirely outpatient transplantation. However, we would like to point out that severe TLS could also complicate PBSCT using RIC regimens in patients with relatively radiation-sensitive malignancies and high tumor burden.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto/terapia , Trasplante de Células Madre/métodos , Acondicionamiento Pretrasplante/efectos adversos , Síndrome de Lisis Tumoral/diagnóstico por imagen , Irradiación Corporal Total/efectos adversos , Adulto , Humanos , Masculino , Cintigrafía , Trasplante Homólogo , Síndrome de Lisis Tumoral/terapiaAsunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Trasplante de Células Madre/efectos adversos , Enfermedad Aguda , Prueba de Histocompatibilidad , Humanos , Ácido Micofenólico/análogos & derivados , Factores de TiempoRESUMEN
According to recent reports, fast engraftment with minimal transplant-related toxicity and mortality (TRT, TRM) can be achieved by using reduced-intensity preparative regimens in allogeneic hematopoietic stem cell transplantation (HSCT). We report our experience with related (39%) and unrelated (61%) HSCT in 44 high risk patients (AML, ALL, CML, CLL) receiving either busulfan/fludarabine or busulfane/fludarabine/ATG or TBI/fludarabine as reduced-intensity preparative regimens. Organ toxicity was minimal with mild mucositis and no major bleeding. Acute GVHD was recorded in 64% of the patients. Twenty-three patients achieved complete remission after transplantation, and complete chimerism was obtained in all patients with stable engraftment (35 patients). Twenty-nine patients died: 15 due to relapse/progression, 14 due to TRM. Survival with median follow-up of 18.5 months was significantly better in patients with matched related transplants compared to patients with other transplants. However, there was no difference between related and unrelated transplants with regard to engraftment, TRM and GVHD. In conclusion, our results in high-risk patients transplanted in CR or with smoldering leukemia from a related donor are encouraging, although a longer follow-up and a larger group of patients is needed in order to evaluate the role of different reduced-intensity preparative regimens in unrelated and related HSCT.