RESUMO
A patient with acute myeloid leukemia developed disseminated tuberculosis with cerebral involvement in the early phase of induction chemotherapy before allogenic stem cell transplantation. He presented with persisting fever of unknown origin, and initially misinterpreted organ lesions in CT scans.
Assuntos
Febre de Causa Desconhecida , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Tuberculose Miliar/induzido quimicamente , Humanos , Quimioterapia de Indução/métodos , Masculino , Transplante de Células-TroncoRESUMO
The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13 months (range 1-42); median dose was 600 mg (range 100-1200). Fourteen patients (82 %) achieved a complete remission (CR), while 5 patients (29 %) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95 % CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1 month on/1 month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20 months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.
Assuntos
Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Sorafenibe , Sequências de Repetição em Tandem/genética , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Cardiovascular risk factors (CVRF) are frequent among long-term survivors after allogeneic hematopoietic cell transplantation (HCT) but prospective data on CVRF are sparse. We conducted a cross-sectional single center study including patients who underwent a first HCT mostly for hematologic malignancies at our center between 2000 and 2016, surviving at least 1 year. 260 patients (median age 54 years [range 19-78], 40% female) who were median 6 years (range 1-16) after transplantation were included. Most patients (232, 89%) had peripheral blood stem cell transplantation. cGVHD was present in 41% at the time of study inclusion. Prevalence of hypertension, dyslipidemia, and diabetes was 58%, 63% and 9%, respectively. Untreated hypertension, dyslipidemia and diabetes was found in 15%, 35% and 2%. Among patients with treated hypertension, 38% did not have blood pressure controlled to levels ≤140/90 mmHg. 36% patients under lipid-lowering therapy did not reach their LDL target. Multivariable logistic regression analyses showed that age and diabetes increased the likelihood for hypertension and dyslipidemia, whereas body mass index, cGVHD and male sex predicted hypertension only. In summary, CVRF in long-term survivors are frequent and persisting after cessation of immunosuppression. A large proportion of CVRF are either untreated or uncontrolled.
Assuntos
Doenças Cardiovasculares , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Sobreviventes , Adulto JovemAssuntos
Imunossupressores/uso terapêutico , Vacinas contra Influenza/efeitos adversos , Neurite Óptica/induzido quimicamente , Neurite Óptica/tratamento farmacológico , Transplante de Células-Tronco/efeitos adversos , Adulto , Feminino , Humanos , Neurite Óptica/diagnóstico , Resultado do TratamentoRESUMO
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 VidaRESUMO
Systemic adjuvant treatment is an integral component in the treatment of women with early-stage breast cancer and contributes significantly to the reduction of breast cancer-specific mortality. Decisions regarding adjuvant treatment modalities are becoming increasingly complex and demand individualised risk assessments based not only on clinicopathological criteria such as tumour size and axillary lymph node status but also on molecular predictors of the biological behaviour of the cancer. In addition, with the development of targeted therapies targeting HER-2 and with the availability of third generation aromatase inhibitors, new therapeutic options are available and need to be integrated into the treatment algorithms. In this review, we discuss the guidelines and recommendations concerning adjuvant systemic treatment of early-stage breast cancer based on current risk classifications.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Mastectomia , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/genéticaRESUMO
Return to work is critical goal following HSCT. However, late effects may impede return to normal activity after HSCT. In the case of inability to work, patients may need a work disability pension to ensure a reasonable livelihood. This study evaluated inability to work and need for disability pension among long-term survivors and analyzed possible determinants of need for social support. This retrospective, single-center study included all HSCT patients surviving ⩾5 years seen at the outpatient clinic between January 2013 and August 2015. There were 203 patients, median age at HSCT 35 years, and 50 years at time of study; median time between HSCT and study control was 12 years; 178 had allo-HSCT, 187 had a malignant disease. At time of study, 156 (77%) were working full or part-time, 47 (23%) were not working. In total, 76 (37%) survivors were receiving a work disability pension compared to 3.17% of the Swiss working population. Patients with a disability pension were significantly older at HSCT, were more often living alone, had more active physical and mental late effects, and higher score of fatigue compared to patients without. These findings underline the importance of screening for employment and the social consequences of non-employment in long-term survivors after HSCT.
Assuntos
Avaliação da Deficiência , Pessoas com Deficiência , Emprego , Transplante de Células-Tronco Hematopoéticas , Pensões , Sobreviventes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SuíçaRESUMO
Conventional treatment or autologous transplantation has not been able to achieve long-term remission in patients with multiple myeloma (MM). Nonmyeloablative allogeneic transplantation might offer an option for cure without the high mortality associated with conventional conditioning. Here we present a retrospective analysis of patients with high-risk MM treated with nonmyeloablative allogeneic transplantation. In all, 52 patients with relapsed MM or high-risk features at diagnosis received 2 Gy TBI alone (n=3) or with fludarabine (n=49) as conditioning. Patients were heavily pretreated with a median of eight cycles of conventional chemotherapy and one or more autologous transplants for all but one patient. Regimen-related toxicity was low. Acute graft-versus-host disease II-IV occurred in 37% of patients, and 70% experienced chronic graft-versus-host disease (cGvHD). Median follow-up was 567 days, and transplant-related mortality was 17% in total. Estimated progression-free and overall survival at 18 months was 29.4 and 41.1%, respectively. Patients with cGvHD had a significantly higher progression-free survival, as did patients with up to eight cycles of pretreatment chemotherapy vs those with nine or more. In this highly pretreated patient group, disease control was unsatisfactory and our results suggest that a potential strategy might be to perform allogeneic transplant earlier in the course of the disease.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Feminino , Seguimentos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal TotalRESUMO
In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.
Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo/mortalidade , Adulto JovemRESUMO
Despite the introduction of novel drugs, cure of multiple myeloma remains rare. Allo-SCT can induce long-term remission, but randomized studies in advanced disease are lacking and the influence of novel drugs remains unclear. In our retrospective analysis of all patients with myeloma allografted in Switzerland, 95 patients were transplanted between 1988 and 2011. Most patients were heavily pre-treated, and 53% received novel drugs before transplant. In all, 51% were allografted after relapse or progression. Transplant trends changed over time with an increase in reduced intensity conditioning and unrelated donors. At the time of analysis 47 patients remained alive, with a median follow-up of survivors of 53 months. Acute GVHD II-IV and chronic GVHD (cGVHD) occurred in 49% and 53%, respectively; TRM at 5 years was 18%. Five-year OS and PFS were 51% and 29%, respectively. Patients who received transplant upfront vs after relapse had a significantly better outcome, as well as those who had a related donor and achieved CR post transplant. We found no impact of pre-treatment with novel drugs or cGVHD. Although long-term remission following allo-SCT can be achieved, GVHD and TRM remain major limitations. Our series suggests that benefit is highest when allo-SCT is used early in the disease.
Assuntos
Mieloma Múltiplo/cirurgia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Iron overload contributes to increased transplant-related mortality, and serum ferritin is typically used to detect iron overload. Other iron parameters have received limited attention. We studied serum ferritin, transferrin, transferrin saturation, iron, soluble transferrin receptor (sTfR) and C-reactive protein (CRP) levels in 230 consecutive patients undergoing myeloablative allo-SCT. All iron parameters were significantly associated with survival. When analyzed individually, both sTfR and transferrin saturation were superior in prognostic power to ferritin (areas under the curve in receiver operating characteristic analysis: 0.670, 0.715, and 0.657, respectively). A combination of ferritin and transferrin saturation had the highest prognostic power: Patients with ferritin below the 30th percentile (<802 ng/mL) showed excellent survival (70±6% at 5 years), while transferrin saturation above the 80th percentile (≥69%) pointed to a high risk of transplant failure (5-year survival 5±5%). The remaining patients showed an intermediate outcome (5-year survival 52±5%). The prognostic impact of iron parameters was independent of other factors such as stage, conditioning regimen and CRP level, and operated similarly across diseases. Iron overload strongly influenced the outcome of allo-SCT. Low pre-transplant ferritin levels indicate a population at low risk, high transferrin saturations and a subgroup of patients with very poor outcome.
Assuntos
Ferro/sangue , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Proteína C-Reativa/metabolismo , Intervalo Livre de Doença , Feminino , Ferritinas/sangue , Seguimentos , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/mortalidade , Masculino , Pessoa de Meia-Idade , Receptores da Transferrina/sangue , Fatores de Risco , Taxa de Sobrevida , Transferrina/metabolismo , Transplante HomólogoRESUMO
Invasive fungal disease (IFD) remains a significant cause of mortality in haematology patients. Management strategies range from empiric therapy to pre-emptive approaches. Prophylaxis with mould-active agents has been evaluated, but the optimal strategy remains unclear. We present here a retrospective analysis of the pre-emptive strategy implemented at our institution. We analysed 348 consecutive neutropenic episodes in 234 patients. The main elements of our pre-emptive strategy included twice-weekly Galactomannan testing and weekly computed tomography (CT) scan. Antifungal prophylaxis usually consisted of fluconazole (400 mg once weekly). Antifungal treatment was started if criteria for IFD (including possible) were fulfilled. Along with the incidence of antifungal treatment and IFD, we also analysed the adherence to the strategy. Adherence was good but suboptimal with 81% of CT scans having been performed at an interval of 10 days or less. Concerning antifungal treatment, in 56 episodes the patient was receiving a mould-active agent as secondary prophylaxis. Antifungal treatment was started during 39% of the remaining episodes. In all, 109 cases of IFD were diagnosed, 51 being probable or proven. Forty-nine patients died before day 100, IFD directly caused or contributed to death in six patients. Two cases of IFD were diagnosed post-mortem and were missed by our pre-emptive strategy. Our pre-emptive strategy is feasible and safe with an acceptable rate of IFD and associated mortality, while avoiding anti-fungal treatment in a significant proportion of patients. The exact role of pre-emptive treatment compared with systematic mould-active prophylaxis can only be determined in a well-designed randomized trial.
Assuntos
Pesquisa sobre Serviços de Saúde , Micoses/diagnóstico , Micoses/tratamento farmacológico , Política Organizacional , Adolescente , Adulto , Idoso , Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Feminino , Galactose/análogos & derivados , Fidelidade a Diretrizes/estatística & dados numéricos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Hospedeiro Imunocomprometido , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Micoses/mortalidade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemAssuntos
Institutos de Câncer , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Suíça/epidemiologiaRESUMO
Hematopoietic SCT (HSCT) after non-myeloablative conditioning is associated with reduced TRM, and increased risk of graft rejection. Although preclinical data have shown the importance of post transplant immunosuppression in achieving engraftment, little is known about the role of CSA in the clinical setting of non-myeloablative transplantation. In a retrospective analysis of patients treated with allogeneic HSCT after fludarabine and 2 Gy TBI, 15 of 77 evaluable patients (20%) experienced primary (n=2) or secondary graft rejection at a median of 66 days post transplant. Mean day 1-28 CSA trough levels were inversely associated with day 28 chimerism (median 99, 85 and 70% for mean CSA <300, 300-600 and >600 ng/mL, respectively; P=0.003). A similar association was observed for the cumulative incidence of graft rejection, which occurred in 8% (<300 ng/mL), 26% (300-600 ng/mL) and 50% (>600 ng/mL, P=0.005) of patients. The detrimental effect of high CSA levels on engraftment was confirmed in multivariable models and was found to operate comparably in sibling and unrelated donor transplants. Impairment of donor T-cell function by high serum levels of CSA might account for this finding, which should be verified in a larger patient group to better understand the role of CSA in non-myeloablative transplantation.
Assuntos
Ciclosporina/efeitos adversos , Rejeição de Enxerto/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/análogos & derivados , Adulto , Idoso , Ciclosporina/administração & dosagem , Ciclosporina/sangue , Feminino , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Vidarabina/uso terapêutico , Irradiação Corporal TotalRESUMO
Rapid recovery of lymphocytes after T-cell depleted hematopoietic SCT (HSCT) protects from relapse of myeloid malignancies. Whether lymphocyte reconstitution has a similar role after non-manipulated transplantation is controversial. We assessed numbers of CD4 and CD8 T-cells, natural killer (NK) cells and B-cells, before and 1, 3, 6, 12 and 24 months after T-cell replete transplantation in 345 patients. Lymphocyte subset counts up to 6 months post transplant had no effect on relapse. Elevated number of NK cells 12 months post transplant protected from relapse. As a novel finding, early recovery of NK cells was associated with significant protection from TRM already at the 3 and 6 months time points (P=0.03, P=0.02). In Cox multivariable models, patients with NK cells above 150/µL were significantly protected from TRM (hazard ratio (HR) 0.45, 95% confidence interval (95% CI) 0.21-0.95, P=0.03), an effect comparable in magnitude with that of carrying >200 CD4 T-cells/µL (HR 0.37, 95% CI 0.19-0.74, P=0.005). CD8 T-cell and B-cell recovery did not affect the rates of relapse or TRM. Early reconstitution of NK cells and CD4 T-cells in patients undergoing T-cell replete HSCT independently protected from TRM. Only a weak protection from disease relapse was noted for patients with high numbers of NK cells, and this occurred only late after transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Linfócitos T/imunologia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Treatment strategies for relapsed/refractory AML are limited and disappointing. Recently, high-dose melphalan (HDM) chemotherapy and autologous hematopoietic SCT (HSCT) has been proposed for AML re-induction. We investigated the impact of HDM remission induction in highly advanced relapsed/refractory AML patients planned for allogeneic HSCT. A total of 23 patients with relapsed/refractory AML were prospectively scheduled for HDM with or without stem cell support followed by myeloablative allogeneic HSCT. Patients included nine individuals with a history of previous HSCT (seven allogeneic, two autologous). A total of 18 patients (78%) achieved a leukemia-free state and an additional four had substantial reduction of the initial leukemia burden warranting treatment continuation. There were no differences between patients with or without immediate stem cell support regarding mucositis or other organ toxicity. A total of 20 patients proceeded to myeloablative allogeneic HSCT. Outcome of allogeneic HSCT was poor: 11 patients (55%) relapsed, 7 patients (35%) died from TRM and only 2 patients (10%) were alive at the last follow-up. Our study shows that HDM is effective in inducing a leukemia-free state in patients with highly advanced relapsed/refractory AML. Leukemia burden reduction with HDM, however, did not translate into improved OS.
Assuntos
Leucemia Mieloide Aguda/terapia , Melfalan/administração & dosagem , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Recidiva , Indução de Remissão/métodos , Transplante Autólogo , Resultado do TratamentoRESUMO
BU-CY is the established non-TBI-based myeloablative conditioning regimen for allogeneic hematopoietic SCT. However, liver toxicity and hepatic veno-occlusive disease (VOD) are frequent life-threatening complications. Pharmacological considerations suggest that BU can trigger toxicity of subsequent CY. Recent animal data confirmed this hypothesis. Less liver toxicity and better outcomes were observed when mice were treated with the reversed order of CY and BU. We analyzed in this study liver toxicity and outcome in patients receiving BU-CY (16 patients) or CY-BU (59 patients). Liver function differed significantly with higher levels of liver function tests between day +10 and +30, and a higher cumulative incidence of VOD in the BU-CY cohort (2/16 (12.5%) vs 0/59 (0%), P=0.006). TRM was significantly higher in patients receiving BU-CY (cumulative incidence BU-CY 45%, CY-BU 17%, P=0.02), without yet translating into a significant survival difference (incidence for survival: BU-CY 38%, CY-BU 63%; hazard ratio 1.19 for BU-CY, 95% confidence interval 0.29-4.82, P=0.80). Rates of engraftment and relapse were not different. These data support the concepts derived from animal models in favor of CY-BU compared with traditional BU-CY and form the basis for prospective controlled comparisons.
Assuntos
Bussulfano/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclofosfamida/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/induzido quimicamente , Fígado/efeitos dos fármacos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Idoso , Bussulfano/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Esquema de Medicação , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Hepatopatia Veno-Oclusiva/imunologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Adulto JovemAssuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia , Quimeras de Transplante/sangue , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Doença Crônica , Feminino , Seguimentos , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Humanos , Cinética , Leucemia/sangue , Leucemia/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Non-myeloablative allogeneic stem cell transplantation followed by immunomodulatory therapies is considered a potentially curative approach in the treatment of multiple myeloma and most effective in a minimal residual disease setting. PATIENTS AND METHODS: The aim of this study was to find the most sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to quantify the tumour load of 11 patients with multiple myeloma after non-myeloablative allogeneic transplantation. Patient-allele specific primers (ASO) and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four different approaches of primer combinations were tested. RESULTS: ASO-forward and -reverse primers together with the clone-specific TaqMan probe were the most sensitive approach compared with the JH (P=0.071) or the FR3 consensus primer (P <0.001). The detection limit amounted to 1/10(4)-1/10(5) cells. Consecutively, 120 samples from 11 patients prior and post allogeneic transplantation were analysed. Three patients reached complete clinical remission accompanied by molecular remission. Disease progression or relapse was seen in six patients. In five, molecular progressive disease was detected prior to the clinical diagnosis of progression or relapse. CONCLUSION: Patient-specific real-time IGH-PCR provides the opportunity for earlier treatment intervention.