RESUMO
Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was 18218.9 compared to 23707.8, 20677.3 and 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.
Assuntos
Medicamentos Biossimilares , Linfoma , Mieloma Múltiplo , Humanos , Filgrastim/efeitos adversos , Lenograstim , Mieloma Múltiplo/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Linfoma/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos , Transplante de Células-Tronco , Proteínas Recombinantes , Mobilização de Células-Tronco HematopoéticasRESUMO
Ruxolitinib is approved for polycythemia vera (PV) patients after failure to previous cytoreductive therapy, based on durable results observed in phase 3 trials. We report a multicenter retrospective study demonstrating the efficacy and safety of ruxolitinib in real-life setting. Eighty-three patients were evaluated. Median follow-up was 24.5 months (IQR 14.0-29.3). At a 3-month response assessment, ruxolitinib provided significant benefit in reducing hematocrit (HCT) level (p < 0.001), phlebotomy requirement (p < 0.001), leucocytes (p = 0.044), and disease-related symptoms (p < 0.001). The exposure-adjusted rates (per 100 patient-years) of infectious complications, thromboembolic events, and secondary malignancies were 6.9, 3, and 3.7, respectively. Non-melanoma skin cancers (NMSC) were the most frequent (40%) SM type. Lymphoproliferative disorders were not detected. Five (6%) patients permanently discontinued ruxolitinib treatment and four (5%) evolved in myelofibrosis (MF), but none in acute leukemia. The rate of MF evolution per 100 patient-years of exposure was 2.8. In our experience, ruxolitinib confirmed its efficacy and safety outside of clinical trials.
Assuntos
Policitemia Vera , Mielofibrose Primária , Humanos , Concentração de Íons de Hidrogênio , Nitrilas/uso terapêutico , Policitemia Vera/complicações , Mielofibrose Primária/diagnóstico , Pirazóis/efeitos adversos , Pirimidinas , Estudos RetrospectivosRESUMO
Unlike allogeneic transplant, autologous stem cell transplantation (ASCT) represents a procedure with a low-risk of cytomegalovirus (CMV) symptomatic reactivation-infection/end-organ disease (CMV complications) and invasive fungal disease (IFD). However, novel drugs for the treatment of lymphoproliferative malignancies could cause an increase of such opportunistic infections, even after ASCT. To the best of our knowledge, there are no published data demonstrating an association between CMV and IFD in the autologous setting, while this association has been widely reported in allogeneic transplantation. We have reviewed our series of 347 ASCT in myeloma and lymphoma patients performed over a period of 14 years with the aim of investigating the descriptive and analytical epidemiology of bacterial, CMV and IFD complications, focusing on the association between CMV and IFD. Patients with myeloma have significantly fewer bacterial infections and IFD than patients with lymphoma, but a similar rate of CMV complications. Descriptive epidemiological data are consistent with the literature, indicating an overall incidence of 36%, 3.5% and 15.5% for bacterial infections, IFD and CMV complications, with a case mortality rate of 4%, 16.7% and 3.7%, respectively. A strong correlation between CMV and IFD exists, with 8 cases of IFD out of a total of 12 presenting a CMV complication. At multivariate analysis, a diagnosis of lymphoma, ≥3 previous treatment lines and age ≥60 years were found to be independent risk factors for IFD. Duration of neutropenia (ANC < 500/mm³) ≥7 days represents an independent risk factor for CMV complications, where neutropenia most likely represents a crude surrogate biomarker indicating a deeper and longer state of overall immunosuppression. From our data we conclude that (1) myeloma patients are at lower risk of bacterial infections and IFD as compared with lymphoma patients but are at equal risk of CMV complications, most likely as a consequence of a selective impact of bortezomib on Herpes Viruses infection control; (2) a significant association exists between CMV and IFD, although a possible cause-effect relationship remains to be determined; (3) IFD is a rare complication after ASCT but burdened by a mortality rate of about 17%, with peak rates in older lymphoma patients who underwent more intensive therapeutic regimens.
Assuntos
Infecções por Citomegalovirus/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/complicações , Transtornos Linfoproliferativos/microbiologia , Transtornos Linfoproliferativos/virologia , Infecções Oportunistas/complicações , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Transplante Autólogo/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Randomized trials comparing chemomobilization efficiency between lenograstim and biosimilar filgrastim are lacking. Our previous retrospective study suggested that lenograstim could be more effective than biosimilar filgrastim when used at the same conventional dosage (5 µg/kg) only in lymphoma patients undergoing peripheral blood stem cell mobilization. We planned a prospective randomized study comparing lenograstim 5 µg/kg with biosimilar filgrastim 10 µg/kg to verify the hypothesis of lenograstim superiority even at half the dosage (stress test). Herein we report data after enrolling 60% of planned patients. STUDY DESIGN AND METHODS: From October 2014 to November 2017, a total of 42 of 70 planned patients with lymphoma were randomly assigned to receive lenograstim 5 µg/kg (21) or biosimilar filgrastim 10 µg/kg (21). Patients were stratified according to treatment line at the time of mobilization (1 or ≥2). Primary endpoint was the rate of achievement of the CD34+ cell collection target dose (≥ 4 × 106 /kg). An improvement by 23% was expected to validate the hypothesis of lenograstim superiority. RESULTS: The two cohorts were balanced for all the baseline features. We observed an identical rate of patients able to reach the targeted CD34+ cell dose and of mobilization failures (90.4 and 4.8% in both cohorts) and a perfect equivalence in any of the secondary collection outcomes. The hypothesis of lenograstim superiority was not corroborated at interim analysis. CONCLUSION: Lenograstim at conventional dosage has failed to demonstrate its superiority over biosimilar filgrastim at double the dosage at interim analysis in their first head-to-head trial.
Assuntos
Filgrastim/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Lenograstim/administração & dosagem , Linfoma/terapia , Adulto , Idoso , Antígenos CD34 , Antineoplásicos/uso terapêutico , Feminino , Humanos , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/citologia , Resultado do TratamentoRESUMO
Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a "probable" IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Nitrilas/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Administração Oral , Antifúngicos/farmacocinética , Aspergilose/patologia , Aspergillus flavus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cromatografia Líquida de Alta Pressão , Monitoramento de Medicamentos , Feminino , Meia-Vida , Humanos , Hospedeiro Imunocomprometido , Nitrilas/sangue , Nitrilas/farmacocinética , Piridinas/sangue , Piridinas/farmacocinética , Espectrometria de Massas em Tandem , Triazóis/sangue , Triazóis/farmacocinética , Voriconazol/efeitos adversos , Voriconazol/uso terapêutico , Adulto JovemRESUMO
We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.
Assuntos
Antineoplásicos/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imidazóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Piridazinas/uso terapêutico , Adulto , Medula Óssea/patologia , Proteínas de Fusão bcr-abl/genética , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Mutação , Neoplasia Residual , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Dermatopatias/etiologia , Transplante HomólogoRESUMO
BACKGROUND: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment. MATERIALS AND METHODS: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR)3.0 and to improve Health-Related Quality of Life (HRQoL) in CML elderly patients. RESULTS: A total of 215 patients in stable MR3.0/MR4.0 were randomized to receive an intermittent TKI schedule 1 month ON-1 month OFF for 3 years (FIXED arm; n = 111) vs. a progressive de-escalation TKI dose up to one-third of the starting dose at the 3rd year (PROGRESSIVE arm; n = 104). Two hundred three patients completed the 3rd year of OPTkIMA study. At the last follow-up, MR3.0 loss was 27% vs. 46% (P = .005) in the FIXED vs PROGRESSIVE arm, respectively. None of these patients experienced disease progression. The 3-year probability of maintaining the MR3.0 was 59% vs. 53%, respectively (P = .13). HRQoL globally improved from the baseline to the 3rd year, without any significant difference between the 2 arms. After the 3rd year, the proportion of patients who was address to TKI discontinuation in the 2 arms was 36% (FIXED) vs. 58% (PROGRESSIVE) (P = .03). CONCLUSIONS: The intensification of intermittent TKI therapy is associated with a higher incidence of MR3.0 loss, but those patients who maintain the MR3.0 molecular response at the end of the study have been frequently considered eligible for TFR. The HRQoL generally improved during the de-escalation therapy in both randomization arms.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Inibidores de Proteínas Quinases , Qualidade de Vida , Humanos , Idoso , Masculino , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Feminino , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Itália , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
BACKGROUND: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. METHODS: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0 ) and to improve Health Related Quality of Life (HRQoL). RESULTS: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0 /MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). CONCLUSIONS: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0 /MR4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Itália , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Sexuais , Fatores de TempoAssuntos
Medicamentos Biossimilares/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/química , Química Farmacêutica , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/química , Neoplasias Hematológicas/terapia , Humanos , Itália , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Transplante AutólogoRESUMO
OBJECTIVES: Polyneuropathy (PN) is a frequent and significant clinical manifestation of multiple myeloma that may be observed at onset of disease or induced during treatment as a therapy-related complication. Polyneuropathy may be a relevant issue in myeloma patients owing to its significant impact on the quality of life, considering that it may lead to dose reduction or treatment discontinuation. The present retrospective study intended to evaluate efficacy of pregabalin (PGB) in treatment of PN in multiple myeloma patients. MATERIALS AND METHODS: Medical charts of 108 consecutive PN myeloma patients were reviewed. Data regarding the tumor history and therapy as well as the clinical and neurophysiological examinations 6 months before and after initiation of PGB therapy were collected. RESULTS: Thirty-eight medical charts had all the requested information. All patients (n = 38) underwent bortezomib-based treatment; 19 were previously treated and 19 were treatment naive. At first neurologic visit, all patients had PN symptoms (grade 2 of National Cancer Institute-Common Toxicity Criteria) without relevant pain. Neurophysiological evaluation showed a significant decrease in sensory nerve action potential amplitude (P = 0.006), conduction velocity (P = 0.006), and distal latency (P = 0.03) of sensory nerves between the first and the last neurological examination, in all patient population. Similar results were observed in treatment-naive patients, when the study cohort was stratified according to previous treatment. On the contrary, no significant differences were found between the first and the last neurophysiological follow-up evaluation in previously treated patients. Six months after PGB treatment, all patients reported disappearance of neurological symptoms (grade 0 National Cancer Institute-Common Toxicity Criteria). CONCLUSIONS: In this retrospective study, improvement in neurological symptoms during PGB therapy was observed in the total population, despite the presence of a distal, sensory axonal neuropathy, as evidenced by neurophysiological examination.
Assuntos
Polineuropatias/tratamento farmacológico , Pregabalina/uso terapêutico , Adulto , Idoso , Bortezomib/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Polineuropatias/etiologia , Estudos RetrospectivosRESUMO
Few data are available on the treatment with DFX in patients with transfusion dependent Ph- Myeloproliferative Neoplasms in fibrotic phase. Here we report 48MPNpatients and iron overload treated with DFX. Starting DFX dose was 20 mg/Kg in 23 patients, 15 mg/Kg in 20 patientsand 10 mg/Kg in 5 patients. After a median treatment of 27.6 months, 5 patients achieved ferritin<500 ng/ml, 11 < 1000 ng/ml and 3 a reduction >50% of basal ferritin with a global response rate of 41%. As to hematological improvement, 9/47 patients (19.1%) showed a persistent rise of Hb>1.5 g/dl, with disappearance of transfusion requirement in 6 cases. The median OS from DFX initiation in patients with chelation response was 61.0 months compared to 15.8 months in patients without chelation efficacy. Treatment with DFX is feasible and effective in MPN with iron overload and a hematological improvement can occur in a sizeable rate of patients.
Assuntos
Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Transtornos Mieloproliferativos/complicações , Idoso , Biomarcadores , Deferasirox/administração & dosagem , Feminino , Ferritinas , Humanos , Ferro/metabolismo , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoRESUMO
To assess the role of platelet (PLT) count for thrombotic complications in Essential Thrombocythemia (ET), 1201 patients followed in 11 Hematological centers in the Latium region were retrospectively evaluated. At multivariate analysis, the following factors at diagnosis were predictive for a worse Thrombosis-free Survival (TFS): the occurrence of previous thrombotic events (p=0.0004), age>60years (p=0.0044), spleen enlargement (p=0.042) and a lower PLT count (p=0.03). Receiver Operating Characteristic (ROC) analyses based on thrombotic events during follow-up identified a baseline platelet count of 944×109/l as the best predictive threshold: thrombotic events were 40/384 (10.4%) in patients with PLT count >944×109/l and 109/817 (13.3%) in patients with PLT count <944×109/l, respectively (p=0.04). Patients with PLT count <944×109/l were older (median age 60.4years. vs 57.1years., p=0.016), had a lower median WBC count (8.8×109/l vs 10.6×109/l, p<0.0001), a higher median Hb level (14.1g/dl vs 13.6g/dl, p<0.0001) and a higher rate of JAK-2-V617F positivity (67.2% vs 41.6%, p<0.0001); no difference was observed as to thrombotic events before diagnosis, spleen enlargement and concomitant Cardiovascular Risk Factors. In conclusion, our results confirm the protective role for thrombosis of an high PLT count at diagnosis. The older age and the higher rate of JAK-2 V617F positivity in the group of patients with a baseline lower PLT count could in part be responsible of this counterintuitive finding.
Assuntos
Contagem de Plaquetas/instrumentação , Trombocitemia Essencial/sangue , Trombose/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Trombocitemia Essencial/patologia , Trombose/patologia , Adulto JovemAssuntos
Anticorpos Monoclonais , Antígenos CD20 , Vacina BNT162 , COVID-19 , Linfoma de Células B , Linfoma não Hodgkin , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Vacina BNT162/administração & dosagem , COVID-19/imunologia , COVID-19/prevenção & controle , Seguimentos , Linfoma de Células B/sangue , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/virologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/virologia , PrognósticoAssuntos
Antineoplásicos/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Feminino , Humanos , Leucemia Promielocítica Aguda/patologia , Leucemia Promielocítica Aguda/fisiopatologia , Leucemia Promielocítica Aguda/prevenção & controle , Recidiva , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: The achievement of complete response (CR) significantly correlates with a better clinical outcome in multiple myeloma (MM) patients treated with autologous stem cell transplant (ASCT). The depth of response is one of the most relevant factors to predict patient's outcome, however the definition of CR through standard criteria has shown several limitations. METHODS: In this study we evaluated the minimal residual disease (MRD) in 50 consecutive MM patients who underwent an up-front tandem ASCT in our center, using a single-tube six-colors flow cytometry assay (FC) based on intra-cytoplasmic immunoglobulin (cy-Ig) light chains ratio evaluated on patient-specific plasma cells (PC) immune profile, in a real-life setting. RESULTS: With a sensitivity up to 10(-5), clonal-PC were documented by FC in 36.4% (12/33) of patients in conventional CR after second transplant. The number of flow MRD-negative patients significantly increased after induction and first ASCT, but not between first and second transplant. The 5-years progression-free survival (5ys-PFS) of flow MRD-negative patients after second transplant was significantly better than patients who remained MRD-positive considering both all patients (5ys-PFS: 70% vs 5%) and patients in CR according to standard criteria (5ys-PFS: 67% vs 0%). CONCLUSIONS: FC remission through cy-Ig light ratio on PC sub-populations is a sensitive, highly informative, low-cost and routinely applicable MRD assay, a powerful tool in treatment response evaluation and a crucial marker of outcome in MM.
Assuntos
Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Cadeias Leves de Imunoglobulina/metabolismo , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Citometria de Fluxo/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Análise de Sobrevida , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
AIM: To determine the incidence of and the risk factors for cytomegalovirus (CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation (ASCT). METHODS: A total of 327 consecutive non CD34(+) selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome (Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin's lymphoma and Hodgkin's lymphoma. The patients who underwent an ASCT for an acute leukemia (n = 20) in the same period were excluded from this analysis. CMV DNA load in the blood has been determined by polymerase-chain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed. RESULTS: Overall, 36 patients (11%) required a specific antiviral treatment for a symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in IgG seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplant-related mortality was significantly higher in patients who experienced a CMV reactivation (8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pre-transplant HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkin's lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy (P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pre-transplant HBcIgG seropositivity (OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell non-Hodgkin's lymphoma (OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation. CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBcIgG seropositivity and a diagnosis of T-cell non-Hodgkin's lymphoma should be considered as independent predictor factors of CMV reactivation.
Assuntos
Aspergillus/genética , Líquido da Lavagem Broncoalveolar/microbiologia , Doenças Hematológicas/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
From this retrospective single center analysis adults with acute lymphoblastic leukemia transplanted in > or 2nd CR from an HLA-identical sibling later than 1993 had a worse outcome. As the transplanted-related mortality improved by time,this result was essentially due to the increased relapse rate. The intensity of the pre-transplant salvage chemotherapy was identified as the main factor influencing the post-transplant relapse-risk.