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1.
Br J Haematol ; 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064595

RESUMO

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a 'borderline' (BL) percentage of mutations (i.e. 97-97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL-CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M-CLL (n = 338) and significantly longer than that of UM-CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL-CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL-CLL remained comparable to that of M-CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL-CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL-CLL: n = 47, 4·3%). BL-CLL at diagnosis showed a biological profile comparable to that of M-CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL-CLL is good and similar to that of M-CLL, with the exception of subset #2 cases.

3.
Expert Opin Pharmacother ; 21(1): 29-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31738609

RESUMO

Introduction: Regimens involving intensive immuno-chemotherapy, followed by high-dose therapy and autologous stem cell transplant represent the standard treatment for younger fit patients with mantle cell lymphoma (MCL). Targeted approaches (i.e. ibrutinib, bortezomib, and lenalidomide) represent the backbone of therapy for relapsed cases.Areas covered: Acalabrutinib is a novel small molecule with a butynamide moiety specifically designed to irreversibly inhibit Bruton tyrosine kinase (BTK), which is more potent and selective than ibrutinib. Relevant publications have been identified through literature searches using the terms 'mantle cell lymphoma' and 'acalabrutinib'.Expert opinion: Acalabrutinib has been approved for the treatment of relapsed/refractory (RR) MCL patients. To date, clinical trials have reported some adverse effects such as cardiac toxicity or atrial fibrillation. Acalabrutinib in combination with other drugs, either in chemo-containing or chemo-free schedules, represent a valid option for MCL. However, none of the treatment schedules containing BTK inhibitors have been shown to be curative in MCL. Acalabrutinib may ultimately represent an option for patients who are 'fit' and exhibit well-controlled disease, which often characterizes only a limited 'niche' among MCL patients.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/administração & dosagem , Linfoma de Célula do Manto/tratamento farmacológico , Pirazinas/administração & dosagem , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Inibidores de Proteínas Quinases/uso terapêutico
4.
Haematologica ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582547

RESUMO

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count>32.0x103/microliter, 1 point. Low, intermediate and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144/395/540/322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era.

5.
Front Oncol ; 9: 528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293969

RESUMO

Minimal residual disease (MRD) in non-Hodgkin's lymphomas (NHLs) still represents matter of interest and debate: indeed, the new available treatments offer higher rates of complete responses and MRD negativity than in the past, with a positive impact on the long-term survival. Furthermore, the introduction of more sensitive and accurate molecular techniques, such as digital PCR (ddPCR) and the next generation sequencing techniques (NGS), increased the possibility of identifying molecular targets to be followed after therapy (such as rearrangement of immunoglobulins, fusion genes, or mutations). This review focused on how molecular biology can help to detect MRD in different types of NHLs and how MRD can change the clinical practice in 2019. In follicular lymphoma (FL), contamination of the grafts and molecular disease persistence after transplantation represent a negative prognostic factors. The combination of Rituximab or Obinutuzumab with Bendamustine seems to be the most effective way to clear MRD in FL patients receiving chemo-immunotherapy (further studies are in progress), and also 90Yttrium-Ibritumomab-Tiuxetan offers a deep clearance of molecular disease. Finally, molecular MRD can further stratify PET-negative cases, with subjects both PET- and MRD-negative presenting the best outcome. In aggressive lymphomas, MRD has a relevant prognostic power and can represent the platform for immunotherapy (such as CAR-T). In diffuse large B-cell lymphoma (DLBCL), the assessment of MRD in the plasma (where cell-free DNA and exosomes circulate) seems to be more predictive than the bone marrow analysis or peripheral blood mononuclear cells. Finally, NGS technologies could be more useful than the classical "patient allele-specific PCR" because they can identify any possible clone emerging during the treatment or follow-up, even if different from that identified at diagnosis, thus predicting relapse. After all, the present available molecular approaches can move MRD from the bench side to the clinical practice.

6.
Cancers (Basel) ; 11(7)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31248056

RESUMO

Chronic Lymphocytic Leukemia (CLL) patients with +12 have been reported to have specific clinical and biologic features. We performed an analysis of the association between demographic; clinical; laboratory; biologic features and outcome in CLL patients with +12 to identify parameters predictive of disease progression; time to treatment; and survival. The study included 487 treatment-naive CLL patients with +12 from 15 academic centers; diagnosed between January 2000 and July 2016; and 816 treatment-naïve patients with absence of Fluorescence In Situ Hybridization (FISH) abnormalities. A cohort of 250 patients with +12 CLL followed at a single US institution was used for external validation. In patients with +12; parameters associated with worse prognosis in the multivariate model were high Lactate DeHydrogenase (LDH) and ß-2-microglobulin and unmutated immunoglobulin heavy-chain variable region gene (IGHV). CLL patients with +12 and high LDH levels showed a shorter Progression-Free-Survival (PFS) (30 months vs. 65 months; p < 0.001), Treatment-Free-Survival (TFS) (33 months vs. 69 months; p < 0.001), Overall Survival (OS) (131 months vs. 181 months; p < 0.001) and greater CLL-related mortality (29% vs. 11% at 10 years; p < 0.001) when compared with +12 CLL patients with normal LDH levels. The same differences were observed in the validation cohort. These data suggest that serum LDH levels can predict PFS; TFS; OS and CLL-specific survival in CLL patients with +12.

7.
J Hematol Oncol ; 12(1): 4, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626425

RESUMO

BACKGROUND: Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis. METHODS: Blood and bone marrow plasma levels of Ang-2, FGF-2, HGF, VEGF, PDGF-ß, IL-8, TNF-α, TIMP-1, and TIMP-2 were determined at diagnosis in MM patients enrolled in the GIMEMA MM0305 randomized controlled trial by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with the type of therapy and patients' characteristics and with a group of non-MM patients as controls. RESULTS: No significant differences were detected between the blood and bone marrow plasma levels of angiogenic cytokines. A cutoff for each CAF was established. The therapeutic response of patients with blood plasma levels of CAFs lower than the cutoff was better than the response of those with higher levels in terms of percentage of responding patients and quality of response. CONCLUSION: FGF-2, HGF, VEGF, and PDGF-ß plasma levels at diagnosis have predictive significance for response to treatment. The stratification of patients based on the levels of CAFs at diagnosis and their variations after therapy is useful to characterize different risk groups concerning outcome and response to therapy. TRIAL REGISTRATION: Clinical trial information can be found at the following link: NCT01063179.

8.
Expert Opin Pharmacother ; 20(5): 487-494, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30608891

RESUMO

INTRODUCTION: Although a variety of therapeutic schemes for Mantle Cell Lymphoma (MCL) have been attempted, the clinical outcome of patients continues to be unsatisfactory especially among patients with a very high-risk profile and in the relapsed/refractory setting. For this reason, recent clinical trials have explored novel approaches, either by the use of biological agents in chemotherapy-free schedules or by integrating them with chemoimmunotherapy regimens. Areas covered: The efficacy of lenalidomide monotherapy and combination therapy established in clinical studies mainly involving relapsed/refractory MCL is reviewed. The mechanism of action of lenalidomide is also discussed. Furthermore, the current position of lenalidomide in the MCL treatment algorithm is debated. Expert opinion: Lenalidomide demonstrated high efficacy and tolerability in several clinical trials as well as in retrospective real-world reports, even in patients who relapsed or were resistant to bortezomib and ibrutinib. In 2013, lenalidomide was approved by the Food and Drug Administration (FDA) for relapsed/refractory MCL after two prior therapies including at least one prior treatment with bortezomib. However, the potential synergistic anti-neoplastic effects of lenalidomide in combination with other biological agents, i.e. ibrutinib and venetoclax, especially in the management of p53-mutated cases, still remain an open issue.


Assuntos
Antineoplásicos/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Humanos , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Resultado do Tratamento
11.
Leukemia ; 32(8): 1869-1873, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29588545
12.
Transfus Apher Sci ; 57(2): 247-249, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29567368

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic anemia (MAHA) defined by mechanical hemolytic anemia, severe thrombocytopenia, and systemic visceral ischemia due to systemic platelet-rich microthrombi. Forty percent of patients with autoimmune TTP experience one or multiple relapses. Patients with refractory TTP are currently managed by corticosteroids, twice-daily PEX, and the anti-CD20 monoclonal antibody rituximab. Herein, we report two cases of severe TTP, refractory to those standard agents. On the basis of the fact that in cases of severe TTP the classical complement pathway is activated, and that the alternative pathway is also involved, both patients underwent eculizumab (anti-C5 monoclonal antibody) therapy. We observed prompt hematological and organ system responses to the eculizumab and the recovery of plasma ADAMTS-13 activity in both cases. Moreover, the fact that both patients discontinued eculizumab, maintaining the response, emphasizes the possibility of its usefulness for limited treatment periods. In conclusion, the diagnostic and therapeutic algorithm in TTP appears complicated by increasing evidence of complement involvement and the eculizumab seems to be a potential agent for refractory patients.


Assuntos
Proteína ADAMTS13/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade
13.
Sci Transl Med ; 10(428)2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29444977

RESUMO

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rß1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rß1 chain when cocultured with activated T cells or CD40L+ cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies.


Assuntos
Interleucina-23/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Receptores de Interleucina/metabolismo , Transdução de Sinais , Microambiente Tumoral , Animais , Anticorpos Neutralizantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Linfonodos/metabolismo , Camundongos , Estadiamento de Neoplasias , Fatores de Risco , Células Estromais/metabolismo , Regulação para Cima
14.
Biol Blood Marrow Transplant ; 24(2): 406-409, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29032267

RESUMO

We report the long-term clinical outcomes of a retrospective multicenter study that enrolled 169 patients with multiple myeloma (MM) in first relapse after failing autologous stem cell transplantation (SCT). After HLA typing at relapse, 79 patients with a suitable donor, 72 (91%) of whom eventually underwent salvage allogeneic SCT (allo-SCT), were compared with 90 patients without a donor who were treated with multiple lines of salvage treatment with bortezomib and/or immunomodulatory agents. At a median follow-up of 30 months (range, 2-180 months) for all patients and 110 months (range, 38-180 months) for surviving patients, 7-year progression-free survival (PFS) was 18% in the donor group and 0% in the no-donor group (hazard ratio [HR], 2.495; 95% confidence interval [CI], 1.770-3.517; P < .0001). Seven-year overall survival (OS) was 31% in the donor group and 9% in the no-donor group (HR, 1.835; 95% CI, 1.306-2.577; P < .0001). By multivariate analysis, chemosensitivity to salvage treatments and presence of a suitable donor were significantly associated with better PFS and OS. The long-term follow-up of this study confirms the significant PFS benefit and provides new evidence of an OS advantage for patients with MM who have a suitable donor and undergo allo-SCT. Allo-SCT should be considered as a treatment option in young relapsed patients with high-risk disease features after first-line treatment.


Assuntos
Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Recidiva , Estudos Retrospectivos , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Doadores de Tecidos , Transplante Autólogo , Transplante Homólogo/mortalidade
16.
Expert Opin Investig Drugs ; 26(11): 1307-1316, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28972395

RESUMO

INTRODUCTION: Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy. Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs. Expert opinion: Data from early clinical trials have shown that venetoclax, as a single agent, is highly effective for relapsed/refractory CLL patients, including those cases with high-risk features. Furthermore, venetoclax seems to be an appropriate option for patients who progress on B-cell receptor (BCR) pathway kinase inhibitors. Venetoclax is also safe, with the most common serious adverse events being neutropenia. The risk of tumor lysis syndrome (TLS) can be reduced by a slow dose ramp-up, careful monitoring, and adequate prophylaxis. Ongoing trials will further clarify the safety and efficacy of venetoclax in combination with other drugs in both relapsed/refractory and untreated CLL patients.


Assuntos
Antineoplásicos/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sulfonamidas/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Relação Dose-Resposta a Droga , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacologia , Síndrome de Lise Tumoral/prevenção & controle
17.
Clin Cancer Res ; 23(23): 7189-7198, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28928163

RESUMO

Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses.Experimental Design: We correlated BCR-ABL/GUSIS and BCR-ABL/ABL transcripts at diagnosis with the outcome-defined by the 2013 European LeukemiaNet recommendations-of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR-ABL/GUSIS and BCR-ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transformation-free (TFS), and overall survival (OS).Results: With a median follow-up of 60 months, 65.4% of patients achieved an optimal response (OR), 5.6% were classified as "warnings," 22.4% failed imatinib, and 6.6% switched to a different TKI because of drug intolerance. We recorded 19 deaths (6.9%), seven (2.5%) attributable to disease progression. We found that higher BCR-ABL/GUSIS levels at diagnosis were associated with inferior rates of OR (P < 0.001), FFS (P < 0.001), and EFS (P < 0.001). Elevated BCR-ABL/GUSIS levels were also associated with lower rates of TFS (P = 0.029) but not with OS (P = 0.132). Similarly, high BCR-ABL/ABL levels at diagnosis were associated with inferior rates of OR (P = 0.03), FFS (P = 0.001), and EFS (P = 0.005), but not with TFS (P = 0.167) or OS (P = 0.052). However, in internal validation experiments, GUS outperformed ABL in samples collected at diagnosis as the latter produced 80% misclassification rates.Conclusions: Our data suggest that high BCR-ABL transcripts at diagnosis measured using GUS as a reference gene identify patients with CML unlikely to benefit from standard-dose imatinib. Clin Cancer Res; 23(23); 7189-98. ©2017 AACR.


Assuntos
Proteínas de Fusão bcr-abl/genética , Regulação Leucêmica da Expressão Gênica , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , /estatística & dados numéricos , Inibidores de Proteínas Quinases/uso terapêutico , Adulto Jovem
18.
Chemotherapy ; 62(6): 353-356, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28810255

RESUMO

We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease in minimal residual disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, 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 treatment was well tolerated and considered safe with easily manageable side effects.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Imidazóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Piridazinas/uso terapêutico , Nucleotídeos de Adenina/administração & dosagem , Adulto , Arabinonucleosídeos/administração & dosagem , Medula Óssea/patologia , Clofarabina , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Imidazóis/efeitos adversos , Imunofenotipagem , Mutação , Neoplasia Residual , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prednisona/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Piridazinas/efeitos adversos , Recidiva , Terapia de Salvação , Transplante Homólogo
19.
Chemotherapy ; 62(6): 350-352, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28743118

RESUMO

We report a case of a chronic myeloid leukemia patient showing progressive bone marrow fibrosis and anemia during imatinib therapy. Given the loss of major molecular response, we switched treatment to dasatinib 100 mg daily, observing a reduction in BCR-ABL transcript, a significant improvement of anemia, and a gradual disappearance of fibrosis. After 7 years of dasatinib therapy the patient maintains a complete cytogenetic response and a deep molecular response; the last bone biopsy confirmed the absence of fibrosis.


Assuntos
Medula Óssea/patologia , Dasatinibe/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 9 , Fibrose , Genes abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Translocação Genética
20.
Clin Lymphoma Myeloma Leuk ; 17(8): 506-512, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28647402

RESUMO

BACKGROUND: Activity-based costing (ABC) was developed and advocated as a means of overcoming the systematic distortions of traditional cost accounting. MATERIALS AND METHODS: We calculated the cost of high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with multiple myeloma using the ABC method, through 2 different care models: the total inpatient model (TIM) and the early-discharge outpatient model (EDOM) and compared this with the approved diagnosis related-groups (DRG) Italian tariffs. RESULTS: The TIM and EDOM models involved a total cost of €28,615.15 and €16,499.43, respectively. In the TIM model, the phase with the greatest economic impact was the posttransplant (recovery and hematologic engraftment) with 36.4% of the total cost, whereas in the EDOM model, the phase with the greatest economic impact was the pretransplant (chemo-mobilization, apheresis procedure, cryopreservation, and storage) phase, with 60.4% of total expenses. In an analysis of each episode, the TIM model comprised a higher absorption than the EDOM. In particular, the posttransplant represented 36.4% of the total costs in the TIM and 17.7% in EDOM model, respectively. The estimated reduction in cost per patient using an EDOM model was over €12,115.72. The repayment of the DRG in Calabrian Region for the ASCT procedure is €59,806. Given the real cost of the transplant, the estimated cost saving per patient is €31,190.85 in the TIM model and €43,306.57 in the EDOM model. CONCLUSION: In conclusion, the actual repayment of the DRG does not correspond to the real cost of the ASCT procedure in Italy. Moreover, using the EDOM, the cost of ASCT is approximately the half of the TIM model.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Custos e Análise de Custo , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pacientes Internados , Pacientes Ambulatoriais , Alta do Paciente , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento
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