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1.
Transfusion ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064638

RESUMO

BACKGROUND: Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals. STUDY DESIGN AND METHODS: Same-day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next-day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14- or 20-hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations. RESULTS: The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change -0.034%; p < 0.01). CONCLUSION: Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results.

2.
Am J Hematol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072687

RESUMO

The t(14;16) translocation, found in 3-5% of newly diagnosed multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n=25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n=223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dl (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor in first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age >60 years (HR=1.65, 95% CI [1.05-2.58]), as well as R-ISS 3 (vs. R-ISS 2; HR=2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival. This article is protected by copyright. All rights reserved.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31932656

RESUMO

In 2015, we implemented an at-home allogeneic haematopoietic cell transplant (allo-HCT) program. Between 2015 and 2018, 252 patients underwent allo-HCT; 41 patients underwent allo-HCT in the at-home program (46% myeloablative; 63% unrelated donor; 32% posttransplant cyclophosphamide), and these patients were compared with 39 in-patients; safety, capacity to release beds for other programs, and economic efficiency cost were evaluated. We observed a lower incidence of febrile neutropenia in the at-home group compared with that in the in-patient group (32% versus 90%; p < 0.0001), whereas the incidence of aspergillosis was similar among groups (at-home 1% versus in-patient 3%; p = 0.5). The at-home patients showed a lower incidence of 1-year severe graft-versus-host disease (GVHD; 10% versus 29%; p = 0.03). There were no differences in 1-year transplant-related mortality, relapse, or overall survival among groups. The re-admission rate in the at-home group was 7%. The at-home setting was less expensive (9087 €/transplant), and its implementation increased capacity by 10.5 allo-HCTs/year. Moreover, a chimeric antigen receptor T-cell program could be established without increasing beds. Thus, our at-home allo-HCT program may be a safe modality to reduce febrile neutropenia and acute GVHD, resulting in lower re-admission rates.

4.
Haematologica ; 105(1): 201-208, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31278209

RESUMO

Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement versus extramedullary plasmacytoma at diagnosis (34.2% vs 19.3%; P=NS.) and relapse (54.5% vs 9%; P=0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 vs 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached vs 46.5 months). Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 13.6 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need.

5.
J Clin Oncol ; : JCO1901231, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770060

RESUMO

PURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31570779

RESUMO

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993-2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p < 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faecium BSI was documented. Among GNB, E. coli, Pseudomonas aeruginosa and K. pneumoniae rates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coli and MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p < 0.001 and p = 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p < 0.001 and p = 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosa infections and rising 30-day mortality rate were documented.

7.
J Med Genet ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31586946

RESUMO

PURPOSE: Patients with Fanconi anaemia (FA), a rare DNA repair genetic disease, exhibit chromosome fragility, bone marrow failure, malformations and cancer susceptibility. FA molecular diagnosis is challenging since FA is caused by point mutations and large deletions in 22 genes following three heritability patterns. To optimise FA patients' characterisation, we developed a simplified but effective methodology based on whole exome sequencing (WES) and functional studies. METHODS: 68 patients with FA were analysed by commercial WES services. Copy number variations were evaluated by sequencing data analysis with RStudio. To test FANCA missense variants, wt FANCA cDNA was cloned and variants were introduced by site-directed mutagenesis. Vectors were then tested for their ability to complement DNA repair defects of a FANCA-KO human cell line generated by TALEN technologies. RESULTS: We identified 93.3% of mutated alleles including large deletions. We determined the pathogenicity of three FANCA missense variants and demonstrated that two FANCA variants reported in mutations databases as 'affecting functions' are SNPs. Deep analysis of sequencing data revealed patients' true mutations, highlighting the importance of functional analysis. In one patient, no pathogenic variant could be identified in any of the 22 known FA genes, and in seven patients, only one deleterious variant could be identified (three patients each with FANCA and FANCD2 and one patient with FANCE mutations) CONCLUSION: WES and proper bioinformatics analysis are sufficient to effectively characterise patients with FA regardless of the rarity of their complementation group, type of mutations, mosaic condition and DNA source.

8.
Blood ; 134(16): 1337-1345, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31484647

RESUMO

Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10-6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.

10.
Biol Blood Marrow Transplant ; 25(11): 2281-2286, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31325586

RESUMO

Diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease relies on the presence of GI symptoms and detection of CMV, mainly by immunohistochemistry (IHC), in GI biopsy specimens. Thus, in a symptomatic patient, a positive CMV-IHC result is accepted as a diagnosis of CMV disease. However, a positive CMV-PCR in GI tissue is considered "possible" CMV disease. Therefore, it would be very useful if, in practice, both techniques showed equal sensitivity and reliability. This is because PCR has many practical advantages over IHC for detecting CMV. The aim of this study was to compare quantitative PCR with IHC for the diagnosis of GI CMV disease. A total of 186 endoscopic GI biopsy specimens from 123 patients with GI symptoms after an allogeneic stem cell transplantation (allo-SCT; 2004-2017) were analyzed by IHC and PCR on 113 paraffin-embedded and 73 fresh samples. The results were then compared. Of the patients with macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, "proven" CMV disease, n = 28), all but 1 were CMV-PCR positive. Of the patients without macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, probable CMV disease, n = 4), only 1 was CMV-PCR positive. Eight patients had CMV-IHC-negative/CMV-PCR-positive gut biopsy specimens. These cases fall within the current definition of possible CMV disease. In 6 of these 8 cases (75%), the viral load in GI tissue was very high (>10,000 copies/µg). Taken together, the results from the proven and probable cases revealed that CMV-PCR shows the same sensitivity (100%), specificity (98%), and positive (93%) and negative predictive value (100%) as CMV-IHC. Detection of CMV in fresh GI mucosa by quantitative PCR is as useful as IHC for the diagnosis of GI CMV disease. The results show that quantitative PCR has the same sensitivity, specificity, and positive/negative predictive value as IHC.

11.
Biol Blood Marrow Transplant ; 25(9): 1703-1712, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31054983

RESUMO

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.

12.
Transfusion ; 59(8): 2636-2642, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31135994

RESUMO

BACKGROUND: Extracorporeal photopheresis (ECP) has been increasingly used as a second-line therapy for graft-versus-host disease (GVHD) but there is no consensus regarding the best therapeutic schedule. STUDY DESIGN AND METHODS: Our offline ECP schedule for treating patients with GVHD was retrospectively reviewed. Patients with acute GVHD were treated on 2 days per week for the first 2 weeks, followed by 1 day per week for 2 more weeks. After the first month of treatment, patients received treatment 1 day every 2 weeks for a minimum of 16 ECP procedures. Patients with chronic GVHD were treated on 1 day per week for 4 weeks followed by 1 day every 2 weeks for a minimum of 14 ECP procedures. RESULTS: Our series comprises 21 (45%) patients with acute GVHD and 26 (55%) patients with chronic GVHD who received 667 ECP procedures. A median (interquartile range [IQR]) of 1.0 (1.0-1.12) total blood volume was processed. Patients with acute and chronic GVHD received ECP procedures during a median of 49 (IQR, 14-103) and 180 (IQR, 111-274) days, respectively. Mild citrate-induced symptoms were present in 98 (46%) and 232 (51%) procedures in patients with acute and chronic GVHD, respectively. Overall response rate (ORR) and overall survival (OS) were 57 and 38% (95% confidence interval [CI], 17%-59%), respectively, for patients with acute GVHD. For patients with chronic GVHD, ORR and OS were 77 and 61% (95% CI, 18%-87%), respectively. CONCLUSION: Our new offline ECP schedule for treating patients with acute and chronic GVHD was efficacious and safe.

13.
Blood ; 133(25): 2664-2668, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31010846

RESUMO

Response criteria for multiple myeloma (MM) require monoclonal protein (M-protein)-negative status on both serum immunofixation electrophoresis (sIFE) and urine (uIFE) immunofixation electrophoresis for classification of complete response (CR). However, uIFE is not always performed for sIFE-negative patients. We analyzed M-protein evaluations from 384 MM patients (excluding those with light-chain-only disease) treated in the GEM2012MENOS65 (NCT01916252) trial to determine the uIFE-positive rate in patients who became sIFE-negative posttreatment and evaluate rates of minimal residual disease (MRD)-negative status and progression-free survival (PFS) among patients achieving CR, CR but without uIFE available (uncertain CR; uCR), or very good partial response (VGPR). Among 107 patients with M-protein exclusively in serum at diagnosis who became sIFE-negative posttreatment and who had uIFE available, the uIFE-positive rate was 0%. Among 161 patients with M-protein in both serum and urine at diagnosis who became sIFE-negative posttreatment, 3 (1.8%) were uIFE positive. Among patients achieving CR vs uCR, there were no significant differences in postconsolidation MRD-negative (<10-6; 76% vs 75%; P = .9) and 2-year PFS (85% vs 88%; P = .4) rates; rates were significantly lower among patients achieving VGPR. Our results suggest that uIFE is not necessary for defining CR in MM patients other than those with light-chain-only disease.


Assuntos
Mieloma Múltiplo/urina , Proteínas do Mieloma/urina , Resultado do Tratamento , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eletroforese/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Blood Cancer J ; 9(4): 36, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30886139

RESUMO

Disease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyzed. Among the 435 patients included in this post-hoc study, 18.6% remained alive and progression free after 5 years of treatment initiation. In these patients, overall survival (OS) rate at 10 years was 60.8% as compared with 11.8% for those progressing within the first 5 years. Hemoglobin (Hb) ≥ 12 g/dl (OR 2.74, p = 0.001) and MGUS-like profile (OR 4.18, p = 0.005) were the two baseline variables associated with long-term disease-free survival. Upon including depth of response (and MRD), Hb ≥ 12 g/dl (OR 2.27) and MGUS-like signature (OR 7.48) retained their predictive value along with MRD negativity (OR 5.18). This study shows that despite the use of novel agents, the probability of disease control at 5 years is still restricted to a small fraction (18.6%) of elderly MM patients. Since this endpoint is associated with higher rates of OS, this study provides important information about diagnostic and post-treatment biomarkers helpful in predicting the likelihood of disease control at 5 years.

17.
Eur J Haematol ; 102(5): 389-394, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719772

RESUMO

OBJECTIVE: The presence of plasmacytomas (Ps) in patients with multiple myeloma (MM) is associated with a poor outcome, both in patients treated conventionally and in patients treated with novel agents. Two types of plasmacytomas have being recognized: paraskeletal plasmacytomas (PPs) and extramedullary plasmacytomas (EMPs), being the incidence of EMPs lower but with worse prognosis. Our aim has been to analyze the efficacy of the pomalidomide-dexamethasone combination in this patient profile. METHOD: In the present study, the efficacy of pomalidomide and dexamethasone in 21 patients from nine hospitals of Catalonia (Spain), with relapsed or refractory MM and Ps, was analyzed. For this purpose, we describe the evolution of paraprotein in serum and urine and the size of plasmacytomas during treatment with pomalidomide-dexamethasone. RESULTS: While 34% of the patients achieved a paraprotein response, only two patients with PPs (9%) responded (RC and PR). There were no responses among patients with EMPs. The median progression-free survival from the start of treatment with pomalidomide/dexamethasone was only 1.7 months and the median overall survival of 4.5 months. CONCLUSION: In conclusion, pomalidomide and dexamethasone has limited efficacy in patients with advanced MM and soft-tissue plasmacytomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/complicações , Plasmocitoma/complicações , Plasmocitoma/tratamento farmacológico , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Mieloma Múltiplo/diagnóstico , Recidiva Local de Neoplasia , Plasmocitoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Talidomida/administração & dosagem , Talidomida/análogos & derivados
18.
Bone Marrow Transplant ; 54(8): 1295-1303, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30664727

RESUMO

Autologous stem cell transplant (ASCT) has demonstrated to be an effective treatment for patients with light-chain (AL) amyloidosis. However, a high transplant-related mortality (TRM) rate was reported in previous series of patients and questioned the role of transplant in this disease. Recently, experienced groups have shown a significant TRM decrease that has been attributed to an accurate selection of patients. Moreover, application of several supportive measures has decreased toxicity over amyloid-involved organs. We analyzed a series of 66 patients with AL amyloidosis, who underwent ASCT at a single institution and evaluated the impact of these measures beyond patient selection. Four temporary groups were established: group-A (non-selection plus post-transplant G-CSF use) with 29 patients, group-B (selection) with 13, group-C (selection and G-CSF avoidance) with 14, and group-D (selection, G-CSF avoidance and corticosteroid's prophylaxis) with 10. A decreasing TRM was observed over time from group-A (38%), to group-D (0%); p = 0.02. We also observed a progressive increase of three-year OS from 62% in group-A to 100% in group-D; p = 0.049. On the multivariate analysis, cardiac involvement was the only independent predictor of survival. Therefore, tailored selection policy together with transplant supportive measures have allowed ASCT to be a safe procedure in AL amyloidosis.

19.
PLoS One ; 13(9): e0203392, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30192814

RESUMO

We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (<0.03 or >32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment.


Assuntos
Cadeias Pesadas de Imunoglobulinas/sangue , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco/métodos , Transplante Autólogo
20.
JAMA Oncol ; 4(10): 1389-1397, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098165

RESUMO

Importance: Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons. Objective: To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis. Data Sources: We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017. Study Selection: By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included. Data Extraction and Synthesis: We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95% credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR). Main Outcomes and Measures: Outcomes of interest were progression-free survival (PFS) and overall survival (OS). Results: Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51-1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups. Conclusions and Relevance: Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Lenalidomida/administração & dosagem , Quimioterapia de Manutenção/métodos , Mieloma Múltiplo/diagnóstico , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
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