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1.
Lancet Infect Dis ; 19(9): 988-1000, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399377

RESUMO

BACKGROUND: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments. METHODS: In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18. FINDINGS: Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p<0·0001) in all patients, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. Humoral and cell-mediated immune responses persisted above baseline until month 13 in all strata and, as expected, vaccine was more reactogenic than placebo (within 7 days after vaccination pain was reported by 221 [79·5%] of 278 vaccine group participants and 45 [16·4%] of 274 placebo group participants; fatigue was reported by 162 [58·3%] of 278 vaccine group participants and 102 [37·2%] of 274 placebo group participants). Incidences of unsolicited or serious adverse events, potential immune-mediated diseases, disease-related events, and fatal serious adverse events were similar between the groups. INTERPRETATION: The immunocompromised adult population with haematological malignancies is at high risk for herpes zoster. The adjuvanted recombinant zoster vaccine, which is currently licensed in certain countries for adults aged 50 years and older, is likely to benefit this population. FUNDING: GlaxoSmithKline Biologicals SA.

2.
Acta Haematol ; : 1-12, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390612

RESUMO

OBJECTIVE: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA). METHODS: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA. RESULTS: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT <31 years (p = 0.010) and prior platelet transfusion <86 U (p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors. CONCLUSION: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30221329

RESUMO

Unfortunately, the original version of this article contained several errors made during final step of article production. In the results section (fourth sentence) of the Abstract, the incomplete sentence,", 31.4% in high-risk group and 4.7% in treatment failure group.

4.
Acta Haematol ; 140(3): 146-156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253397

RESUMO

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. METHODS: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. RESULTS: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015-4.842; p = 0.0458). CONCLUSION: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

5.
Clin Lymphoma Myeloma Leuk ; 18(10): e391-e399, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30082224

RESUMO

INTRODUCTION: BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed. PATIENTS AND METHODS: A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified. RESULTS: In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts. CONCLUSION: These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia.

6.
Eur J Nucl Med Mol Imaging ; 45(13): 2274-2284, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30056546

RESUMO

PURPOSE: The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs. METHODS: We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients. RESULTS: Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort. CONCLUSION: The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs.

7.
Cancer Med ; 7(5): 1766-1773, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29577681

RESUMO

Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP-CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP-CML, the dose-efficacy as well as dose-safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose/BW) and the probability of dose-limiting toxicity (≥grade 3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a significant inverse association was discovered between Dose/BW and the probability of major molecular response (BCR-ABL1/ABL1 ≤ 0.1%) when controlled for sex (P = 0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12-month follow-up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long-term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once daily be tested in patients with newly diagnosed CP-CML.

8.
Korean J Intern Med ; 33(6): 1169-1181, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29295612

RESUMO

BACKGROUND/AIMS: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) is limited. METHODS: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. RESULTS: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). CONCLUSION: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.

9.
Biol Blood Marrow Transplant ; 24(5): 923-929, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29339269

RESUMO

This prospective study evaluated the efficacy and toxicity of intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99 patients with MM, enrolled between January 2013 and March 2016, received intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2) before ASCT. The median time to transplant was 6.2 months, and 90 (90.9%) patients underwent ASCT within 12 months of the diagnosis. The overall response rate after ASCT was 94.0%, including 43.5% with a stringent complete response/complete response, 27.3% with very good partial response, and 23.2% with partial response. The most common severe nonhematologic toxicity (grade 3 to 4) was infection (26.3%) and stomatitis (15.2%). Three (3.2%) patients developed veno-occlusive disease. No treatment-related mortality was observed. After a median follow-up of 26.1 months, the median progression-free survival was 27.2 months (range, 13.0 to 41.4 months) and median overall survival was not reached. In conclusion, a conditioning regimen of intravenous busulfan and melphalan was effective and tolerable. ClinicalTrials.gov. number: NCT01923935.

10.
J Leukoc Biol ; 103(1): 53-66, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28978662

RESUMO

We report the unique role of CX3CL1 (or fractalkine) on CD11b+ myelomonocytic cells expressing CX3CR1, the only known receptor for CX3CL1, in promoting blood perfusion recovery. In a mouse ischemic hind-limb model, CD11b+ CX3CR1+ cells migrated to ischemic femoral muscles through CX3CL1-mediated chemotaxis. CD11b+ CX3CR1+ macrophages isolated from ischemic tissues [tissue (T)-CD11b+ CX3CR1+ ] of muscle exert a proangiogenic effect through platelet factor-4 (CXCL4; PF-4) production. PF-4 does not promote angiogenesis by itself but, instead, increases VEGF-mediated angiogenesis. Despite proangiogenic effects of muscle-derived T-CD11b+ CX3CR1+ macrophages, their clinical implementation is limited because muscle excision is required for cell harvesting. Therefore, we focused on the more accessible bone marrow (BM)-CD11b+ CX3CR1+ monocytes, which migrate from BM into ischemic muscles via CX3CL1-mediated chemotaxis. PF-4 expression was not detected in BM-CD11b+ CX3CR1+ monocytes under normal conditions, but CX3CL1 (50 ng/ml) induced high PF-4 expression and enabled BM-CD11b+ CX3CR1+ monocytes to achieve a similar angiogenic potential to that of T-CD11b+ CX3CR1+ macrophages ex vivo. Furthermore, we were able to identify a subset of monocytes that express CD11b and CX3CR1 in human peripheral blood and confirmed the proangiogenic effect of CX3CL1 treatment. Thus, CX3CL1-treated CD11b+ CX3CR1+ monocytes may be of potential therapeutic use to significantly accelerate recovery of blood perfusion in ischemic diseases.

11.
Oncotarget ; 8(54): 92171-92182, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29190906

RESUMO

The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.

12.
Oncotarget ; 8(54): 92289-92299, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29190915

RESUMO

Despite their critical roles in angiogenesis and host immunosuppression within the tumor microenvironment, the prognostic significance of myeloid-lineage cells expressing CD11b and CX3CR1 in diffuse large B-cell lymphoma (DLBCL) has not been well studied. We prospectively enrolled newly-diagnosed DLBCL patients at two Korean institutions between May 2011 and Aug 2015. CD11b+CX3CR1+ cells were analyzed by flow cytometry using peripheral blood (PB) and bone marrow (BM) aspirate samples before treatments. Eighty-nine patients (52 males) were enrolled. The median age was 65 years (range, 19-88 years). Thirty-seven patients (42%) were classified as high-intermediate or high risk according to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). Patients were categorized into either high or low PB-/BM-CD11b+CX3CR1+ monocyte group according to the cutoffs identified by the receiver-operating-characteristics analysis (PB, 3.68%; BM, 3.45%). The high PB-CD11b+CX3CR1+ monocyte group was significantly associated with high-intermediate and high risk NCCN-IPI group (P = 0.004). With a median follow-up of 27.7 months (range, 1.7-60.4 months), the low PB-CD11b+CX3CR1+ monocyte group showed significantly better overall survival (OS) than the high PB-CD11b+CX3CR1+ monocyte group (3-year, 92.3% vs. 51.2%, respectively; P < 0.001). In contrast, no significant difference was observed between the high and low BM-CD11b+CX3CR1+ monocyte groups. Among patients with high-intermediate to high risk NCCN-IPI, the high PB-CD11b+CX3CR1+ monocyte group showed significantly worse OS than the low PB-CD11b+CX3CR1+ monocyte group (3-year, 29.3% vs. 80.2%, respectively; P = 0.008). Taken together, PB-CD11b+CX3CR1+ monocyte percentage correlates with the NCCN-IPI risk stratification, which enables identification of subgroups with extremely poor clinical outcomes.

13.
Blood Res ; 52(3): 200-206, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29043235

RESUMO

BACKGROUND: Rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) is one of the effective chemotherapeutic regimens for patients with advanced stage marginal zone lymphoma (MZL). However, prognostic factors that affect the outcome of treatment for MZL are not well understood. METHODS: Between August 2006 and June 2013, patients with newly diagnosed stage III and IV MZL treated with R-CVP as a first-line therapy from 15 institutions were retrospectively analyzed. Patients' clinical and laboratory data at diagnosis were collected by review of medical records. RESULTS: A total of 80 patients were analyzed. Bone marrow involvement was observed in 30% cases. Twelve patients (15%) had nodal MZL, and 41.3% patients exhibited multiple mucosa-associated lymphoma tissue sites. Overall response rate was 91.3%, including 73.8% achieving complete response. Advanced MZL patients treated with R-CVP showed a 3-year progression-free survival (PFS) rate of 69.6%. Prognostic markers significantly affecting PFS in univariate analysis were platelet to lymphocyte ratio (PLR, <95 vs. ≥95, P=0.014), serum albumin (≤3.9 vs. >3.9 g/dL, P=0.008), and the International Prognostic Index (IPI) score (1 vs. 2-4, P=0.032). In multivariate analysis, only PLR (<95 vs. ≥95, HR 0.367, 95% CI, 0.139-0.971, P=0.043) was an independent risk factor for PFS. CONCLUSION: PLR ≥95 at diagnosis is an independent prognostic marker for PFS in advanced stage MZL patients treated with R-CVP. This marker may aid clinicians in predicting the response to R-CVP chemotherapy in stage III and IV MZL patients.

14.
Clin Cancer Res ; 23(23): 7180-7188, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28939746

RESUMO

Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP.Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months.Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n = 79) or 400 mg twice-daily (n = 81), or imatinib 400 mg daily (n = 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P = 0.0044 and P = 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P = 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction.Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome-positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289 Clin Cancer Res; 23(23); 7180-8. ©2017 AACR.


Assuntos
Benzamidas/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Pirazinas/uso terapêutico , Adulto , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Esquema de Medicação , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Leucemia Mieloide de Fase Crônica/genética , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Indução de Remissão , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
15.
Oncotarget ; 8(23): 37605-37618, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28402945

RESUMO

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), ß2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP.In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Diarreia/induzido quimicamente , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/etnologia , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , República da Coreia , Resultado do Tratamento
17.
Oncotarget ; 7(44): 72033-72043, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27713132

RESUMO

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/sangue , Lactato Desidrogenases/sangue , Linfoma Difuso de Grandes Células B/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/secundário , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/secundário , Prednisona/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Rituximab/uso terapêutico , Testes Sorológicos/métodos , Vincristina/uso terapêutico , Adulto Jovem
18.
Leuk Res ; 49: 80-7, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27608179

RESUMO

This study retrospectively investigated the optimal timing of radiotherapy (RT) in patients with limited-stage extranodal NK/T-cell lymphoma (ENTKL). Among 158 patients with newly diagnosed stage I/II ENKTL, 61 patients were treated with sequential chemotherapy followed by radiotherapy (SCRT), 55 with concurrent chemoradiotherapy followed by non-anthracycline-based chemotherapy (CCRT/CT), and 42 with chemotherapy (CT) only. The 5-year overall survival (OS) rate did not differ between SCRT (77.7±5.5%) and CCRT/CT (68.9±6.8%; p=0.234). In the SCRT group, 18 patients (29.5%) relapsed within the RT field and 6 (9.8%) at systemic sites, while in the CCRT/CT group, 9 patients (16.4%) relapsed at the primary site and 14 (25.5%) at systemic sites. The 5-year cumulative incidence of relapse (CIR) at primary sites was 26.3% and 19.2% after SCRT and CCRT/CT (p=0.308), while the 5-year CIR of systemic sites was 8.7% and 26.5% after SCRT and CCRT/CT, respectively (p=0.010). In the multivariate analysis, NK/T-cell Prognostic Index score and CR achievement were the most important prognostic factors for survival. Although up-front RT had limitations in systemic disease control and was associated with an increased risk of systemic relapse during RT compared to SCRT, timing of RT did not significantly affect survival outcomes.


Assuntos
Quimiorradioterapia/métodos , Linfoma Extranodal de Células T-NK/terapia , Adolescente , Adulto , Idoso , Terapia Combinada/métodos , Tratamento Farmacológico , Feminino , Humanos , Linfoma Extranodal de Células T-NK/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Oncotarget ; 7(51): 85584-85591, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27542213

RESUMO

We designed a new treatment protocol incorporating concurrent administration of L-asparaginase (to reduce the probability of systemic progression during concurrent chemoradiotherapy (CCRT)) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma, nasal type (ENKTL). CCRT comprised radiation (36-44 Gy) with weekly cisplatin (30 mg/m2) and tri-weekly L-asparaginase (4 000 IU). Chemotherapy-MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2 and Ifosfamide 1 000 mg/m2 on days 2-3, dexamethasone 40 mg on days 1-4, and L-asparaginase 6 000 IU/m2 on days 4, 6, 8, 10)-was repeated every 28 days for two cycles. One of the 28 patients developed distant lesions after CCRT. The final complete response rate was 82.1%. Four patients dropped out during or after their first MIDLE cycle due to toxicities (recurrent G3 hyperbilirubinemia [n = 1], G3-5 increased creatinine [n = 2], and G5 infection [n = 1]). With a median follow-up of 46 months (95% CI: 39-47 months), the estimated 3-year progression-free survival rate and overall survival rate were 74.1% and 81.5%, respectively. This MIDLE protocol may be effective for localized ENKTL. However, concurrent administration of L-asparaginase during CCRT does not seem to provide additional benefits.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Quimiorradioterapia , Linfoma Extranodal de Células T-NK/terapia , Radioterapia Conformacional , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Dexametasona/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Estimativa de Kaplan-Meier , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , República da Coreia , Fatores de Tempo , Resultado do Tratamento
20.
Haematologica ; 101(6): 717-23, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26888022

RESUMO

The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Neoplasia Residual/diagnóstico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Reação em Cadeia da Polimerase , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Recidiva , Retratamento , Fatores de Tempo , Resultado do Tratamento
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