High-dose chemotherapy followed by locoregional irradiation improves the outcome of patients with international neuroblastoma staging system Stage II and III neuroblastoma withMYCN amplification

Cancer ◽  
2004 ◽  
Vol 101 (5) ◽  
pp. 1081-1089 ◽  
Author(s):  
Anne Laprie ◽  
Jean Michon ◽  
Olivier Hartmann ◽  
Caroline Munzer ◽  
Marc-David Leclair ◽  
...  
Keyword(s):  
Staging System ◽  
High Dose Chemotherapy ◽  
Stage Ii ◽  
High Dose ◽  
International Neuroblastoma Staging System

Bortezomib in Multiple Myeloma: Treatment and Retreatment. A Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4819-4819 ◽  
Author(s):  
Antonios G. Bilalis ◽  
Konstantinos Papadimitriou ◽  
Anastasia Pouli ◽  
Konstantinos Papanastasiou ◽  
Seraphem Tsakanikas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Median Time ◽  
Light Chain ◽  
Staging System ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Pulmonary Complications ◽  
High Dose ◽  
Time To Progression

Abstract Introduction: Although major advances have been done in the treatment of multiple myeloma (MM) patients (pts), it still remains incurable with conventional or high dose chemotherapy with autologous stem cell rescue (ASCT). A novel agent which takes standard place in the management of MM pts is bortezomib. Patients and methods: The aim of our study is to evaluate prospectively the response to bortezomib (1.3mg/m2 on days 1, 4, 8, 11 in a 21-day cycle for up to 8 cycles) in MM pts relapsed or refractory after standard therapy. We evaluate its re-administration (with the same schedule) in a number of pts who have relapsed after a complete course of bortezomib as well. We also present the pts who have received bortezomib as maintenance therapy (1.3mg/m2 on days 1 and 4 in a 28-day cycle). Results: From September 2004 until August 2007 36 MM pts have been included. The characteristics of the pts are as follows: 21 males, 15 females, median age at diagnosis 57 years (41–70). Eleven pts was IgGκ, 8 pts IgGλ, 8 IgAκ,3 IgAλ, 3 κ light chain and 3 λ light chain. According to the Durie-Salmon staging system 3 pts was IA, 13 IIA, 16 IIIA and 4 IIIB. The median number of prior therapies was 3 (1–7). Nineteen pts had received ASCT prior to bortezomib. Median time from diagnosis to the first dose of bortezomib was 47 months (5–156). Twenty eight pts received bortezomib for relapse and 8 for refractory disease. Median follow-up time since bortezomib administration was 12 months (1–30). The pts who achieved CR, VGPR or was in PD for two successive cycles discontinued treatment. The median number of cycles received was 5.5 (1–8). The response outcome, according to the International Myeloma Working Group response criteria, for the pts who received up to 4 cycles, was: 7 pts in CR, 5 pts in VGPR, 7 pts in PR, 7 pts in SD, 6 pts in PD, 3 pts died due to PD and 1 due to pulmonary complications. The response outcome for the pts who received up to 8 cycles was: 5 pts in CR, 4 pts in VGPR, 5 pts in PR, 4 pts in SD, 3 pts in PD. The median time to progression for responders was 8 months (1–26). The overall outcome was CR 22.3%, VGPR 16.7%, PR 11.1%, SD 19.4% and PD 30.5%. Ten pts who achieved CR, VGPR or PR continued maintenance therapy with bortezomib. The median time of maintenance therapy until relapse was 7 months (2–16). Six pts from the maintenance group who relapsed re-treated with bortezomib. Also 1 patient who relapsed without receiving bortezomib maintenance re-treated as well. After a median number of 6 cycles (1–8) of re-treatment, 1 patient is in VGPR, 1 in PR, 3 in SD and 2 in PD. Conclusions: We conclude that bortezomib offers an overall response rate of 50.1% (CR, VGPR, PR) in heavily pre-treated MM pts achieved even from the very first cycle. Probably the addition of bortezomib as maintenance therapy may prolong the time to progression in responding pts. Retreatment is also an attractive option, but we cannot extract safe conclusions due to our limited sample size.

Validation of International Staging System (ISS) for Multiple Myeloma: A Retrospective Analysis of 487 Patients at 8 Brazilian Centers.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5069-5069
Author(s):  
Vania T.M. Hungria ◽  
Angelo Maiolino ◽  
Gracia Martinez ◽  
Gisele Colleoni ◽  
Luciana Oliveira ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Median Survival ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
High Dose ◽  
International Staging System ◽  
New System

Abstract Introduction: The survival of patients with multiple myeloma varies from a few months to more than 10 years. This heterogeneity is related to the characteristics of the myeloma itself and of the host. The identification of the factors which influence the prognosis is very important to predict the result, assist in the choice of the treatment and adequately stratify the patients in clinical studies. Many prognostic factors have been identified in patients with multiple myeloma, such as anemia, renal failure, ß2 microglobulin, albumin and chromossomic alterations. Some authors have combined prognostic factors and proposed various systems of staging. However, none of them have yet substituted the Durie-Salmon staging system. Recently, the International Myeloma Working Group, with the objective of developing a simple and reliable staging system, which can be internationally applied to classify and stratify patients with multiple myeloma, identified 3 risk groups. This new system of staging, the “International Staging System” (ISS), consists of stage I: ß2 microglobulin < 3.5 mg/L plus albumin ≥ 3.5 g/dL (median survival: 62 months); stage II: neither I nor III (median 44 months); stage III: ß2 microglobulin > 5.5 mg/L (median 29 months). This study included sites in North America, Europe and Asia, but the sites in Latin America were not included. Objective: To validate the ISS in patients with multiple myeloma at Brazilian centers. Patients and Methods: Four hundred and eighty-seven patients with the diagnosis of multiple myeloma within the period of 1998 to 2004 at Santa Casa de São Paulo, Hospital Universitário Clementino Fraga Filho do Rio de Janeiro, Hospital das Clínicas de São Paulo, Hospital São Paulo, Hospital das Clínicas de Ribeirão Preto, HEMOPE, Hospital Prof. Edgar Santos de Salvador and Hospital de Clínicas de Porto Alegre, with available data on albumin and ß2 microglobulin, were stratified according to the ISS. A total of 339 patients received standard therapy and 148 received high-dose therapy as initial therapy. The survival was estimated using the Kaplan-Meier method with differences in survival examined using the logrank test. Results: The median age of the patients was 60 years, 52% male and 48% female. In Stage I (n=104), the global median survival was not reached, the survival at 60 months was 60%, in stage II (n=264), the global median survival was 61 months and in stage III (n=119), 19 months (p<0.001). Conclusion: The new system of staging for multiple myeloma (ISS) is simple, based on variables easy to be applied and was possible to be validated in patients with multiple myeloma in Brazilian centers.

Rituximab (R) in Addition to Dose-Dense Chemotherapy MegaCEOP and Intensification with R-MAD Followed by High Dose Chemotherapy BEAM with Autologous Stem Cell Transplantation (ASCT) Is Safe and Effective in Untreated High Risk Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1899-1899 ◽  
Author(s):  
Annalisa Chiappella ◽  
Giuseppe Rossi ◽  
Maria Giuseppina Cabras ◽  
Anna Marina Liberati ◽  
Giovannino Ciccone ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
Stage Ii ◽  
High Dose ◽  
Advanced Stage ◽  
Who Grade ◽  
Bulky Disease ◽  
Dose Dense

Abstract Introduction: The addition of R to dose-dense chemotherapy CHOP and to high-dose chemotherapy seems to improve the outcome of advanced stage DLBCL. Patients and methods: From August 2000 to September 2006, 120 previously untreated patients (pts) <61 years affected by aggressive DLBCL were enrolled into 12 GIMURELL centers. Inclusion criteria were: advanced stage II, III-IV with age-adjusted (aa)-IPI score 2–3 or BM involvement (any aa-IPI score), viral markers negativity. Treatment plan consisted in a dose-dense chemoimmunotherapy R-MegaCEOP (R 375 mg/m2 d1, CTX 1200 mg/m2 + EPI 110 mg/m2 + VCR 1.4 mg/m2 d3 and PDN 40 mg/m2 dd3–7) every 14 days with G-CSF support for 4 courses; pts in CR or PR received two courses of intensified chemotherapy R-MAD (Mitoxantrone 8 mg/m2 + ARA-C 2000 mg/m2/12h + Dexamethasone 4 mg/m2/12h dd1–3 and R 375 mg/m2 d4 and before peripheral blood stem cell harvest as in vivo purging) followed by ASCT with BEAM as conditioning regimen ± IF-RT. All pts received antibacterial and antifungal prophylaxis throughout the whole treatment. In pts with BM and/or CNS risk involvement, 4 IT-MTX 15 mg were planned as intrathecal prophylaxis. Results: All 120 pts were evaluable: median age 47 years (19–60); 65 males and 55 females; 6% were at Low-Intermediate, 52% at Intermediate-High and 42% at High risk according to aa-IPI score; PS ≥2 65%, 27% BM involvement, 48% bulky disease, 80% LDH >normal and stage II/III/IV 8/19/73% respectively. Complete response at the end of treatment was achieved in 98 pts (82%), PR in 5 (4%), 12 (10%) did not respond and 5 (4%) died of toxicity. IF-RT was performed as consolidation of bulky disease or residual disease on 36% of pts. With a median follow-up of 42 months, 4-yr FFS and 4-yr OS rates were: 77% and 80%. In 101 pts (84%), PBSC yeald was good, with a median of 9.7 × 106 cells CD34/kg (range 2.5–56.3). Nineteen pts (16%) were not autografted: 5 because of inadequate PBSC yield, 9 of progression disease and 5 of toxicity. All 101 pts who underwent ASCT achieved a complete hematological engraftment with a median of 9 days (3–27) to neutrophil counts >0.5 × 109/L and a median of 14 days (1–72) to a self-sustaining platelet count >50 × 109/L. Transfusional support was: platelets and red-cell package respectively in 8% and 24% of pts during 4 R-MegaCEOP, 92% and 70% during 2 R-MAD and 96% and 74% during BEAM consolidation. Few severe toxicities (WHO grade 3–4) were reported; most frequent (12%) were infection and mucositis during R-MAD and BEAM phase. Five patients died of toxicity due to: E.coli sepsis in 2 pts respectively after R-MegaCEOP and R-MAD, one of sepsis ndd after R-MAD, one of Staphilococcus pneumonia after R-MAD and one of P.aeruginosa pneumonia after BEAM regimen. There are no secondary MDS or ANLL or solid tumour. Conclusions: This study suggests that Rituximab as adjuvant to dose-dense and high dose chemotherapy with ASCT support is effective and safe in high risk DLBCL.

The Role of Irradiation of the Internal Mammary Lymph Nodes in High-Risk Stage II to IIIA Breast Cancer Patients After High-Dose Chemotherapy: A Prospective Sequential Nonrandomized Study

2003 ◽  
Vol 21 (14) ◽  
pp. 2713-2718 ◽  
Author(s):  
Salomon M. Stemmer ◽  
Shulamith Rizel ◽  
Izhar Hardan ◽  
Adamous Adamo ◽  
Avivit Neumann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Electron Beam ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Stage Ii ◽  
High Dose ◽  
Internal Mammary

Purpose: This phase II single-institution prospective, nonrandomized trial investigates high-dose adjuvant chemotherapy and locoregional radiotherapy in patients with breast cancer. We compared the outcome of patients in this study treated with radiotherapy fields including the internal mammary nodes (IMN) to a group of patients who did not receive IMN irradiation. Patients and Methods: 100 patients with high-risk stage II–III breast cancer received doxorubicin-based adjuvant chemotherapy followed by high-dose chemotherapy, stem-cell support, and locoregional radiotherapy. The radiotherapy included electron-beam irradiation to the IMN. For 20 months during the study, no electron-beam facility was available and we were unable to deliver the IMN irradiation as planned to 33 patients. The remaining 67 patients (32 treated before and 35 treated after this period) received IMN irradiation. Patients with receptor-positive tumors received tamoxifen for 5 years. Results: At a median follow-up of 77 months for all of the patients, disease-free survival (DFS) was significantly prolonged in patients receiving IMN radiation compared to those without IMN radiation (73% v 52%; P = .02). A trend was seen for overall survival (OS; 78% v 64%; P = .08). Cox regression multivariate analysis found IMN radiotherapy to be significant both for DFS and OS. Estrogen receptor positivity was also significant for DFS. There was no treatment related mortality. Conclusion: In patients with high-risk stage II to III breast cancer, the inclusion of the IMN in the radiotherapy field was associated with a statistically significant increase in DFS and a borderline increase in OS.

scholarly journals Heparanase Influences Expression and Shedding of Syndecan-1, and Its Expression by the Bone Marrow Environment Is a Bad Prognostic Factor in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3502-3502 ◽  
Author(s):  
Karene Mahtouk ◽  
Dirk Hose ◽  
Thierry Reme ◽  
Michael Hundemer ◽  
Michel Jourdan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mrna Expression ◽  
Extracellular Enzymes ◽  
Staging System ◽  
Myeloma Cell ◽  
High Dose Chemotherapy ◽  
Biologically Active ◽  
High Dose ◽  
High Level

Abstract The heparan sulfate (HS) proteoglycan (PG) syndecan-1 plays a major role in multiple myeloma (MM), in part by concentrating HS-binding growth factors on the surface of MM cells (MMC). The function of HSPG is regulated by extracellular enzymes that modulate the structure of HS-chains. One such enzyme is heparanase (HPSE), an endo-glucuronidase that cleaves HS chains at only a few sites, resulting in fragments of 10–20 sugar units long that are biologically active. Using Affymetrix microarrays and real-time RT-PCR, we showed that the gene encoding HPSE was expressed by 11/19 myeloma cell lines (HMCLs). In HSPE-positive HMCLs, syndecan-1 mRNA expression and production of soluble syndecan-1, unlike expression of membrane syndecan-1, were significantly increased. Downregulation of HPSE by HPSE-siRNA resulted in a decrease of syndecan-1 mRNA expression and soluble syndecan-1 production, without affecting membrane syndecan-1. Contrary to HMCLs, HPSE was expressed in only 4/39 primary MMC samples at a low level, whereas it was highly expressed in 36/39 whole bone marrow (WBM) microenvironment samples. In the latter, HPSE was expressed at a median level in polynuclear cells and T cells, at high level in monocytes and osteoclasts, and it was not expressed in BM stromal cells. In order to investigate the connection of clinical parameters with HPSE gene expression, 30/39 myeloma patients treated with high dose chemotherapy and autologous stem cell transplantation where classified into two groups: 15 patients with the lowest or the highest HPSE expression in the WBM. The HPSEhigh group had an increased percentage of patients with elevated C-reactive protein and β2-microglobulin. According to the international staging system (ISS), the HPSEhigh group included a significant higher frequency of patients with stage III MM and a lower frequency of patients with stage I MM. HPSEhigh patients had a shorter event free survival (EFS) (p=.017) and overall survival (OAS) (p=.023) than HPSElow patients. Classifying these 30 patients into two groups according to HPSE expression in MMC did not yield to any EFS or OAS significant differences between the two groups. Altogether, those data provide evidence that HPSE not only modulate syndecan-1 activity through the cleavage of HS chains but also regulates syndecan-1 mRNA expression and shedding. We report for the first time that the expression of a gene in the BM, i.e. HSPE, is an indicator of poor prognostic for MM patients. Therefore, HPSE inhibitors like PI-88, which is currently in clinical trial, will be of interest for the treatment of patients with MM.

Clinical significance of bone marrow metastases as detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplantation.

1996 ◽  
Vol 14 (6) ◽  
pp. 1868-1876 ◽  
Author(s):  
K K Fields ◽  
G J Elfenbein ◽  
W L Trudeau ◽  
J B Perkins ◽  
W E Janssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Autologous Bone Marrow Transplantation ◽  
Stage Iv ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
Stage Ii ◽  
High Dose ◽  
Chain Reaction ◽  
Polymerase Chain

PURPOSE The present study evaluates the clinical significance of detection of cytokeratin 19 (K19) in the bone marrow of patients with breast cancer undergoing high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS We studied retrospectively cryopreserved bone marrow aspirates from 83 patients with high-risk stage II, III, and IV breast cancer obtained before bone marrow harvest but after induction chemotherapy. All samples were histologically negative for metastases. Polymerase chain reaction (PCR) for K19 was performed according to methods described previously and results were correlated with the probability of relapse following HDCT and ABMT. RESULTS The incidence of occult metastases as defined by PCR for K19 message was 52% for 19 stage II, 57% for 14 stage III, and 82% for 50 stage IV patients (two-tailed P = .0075, chi 2 test). The probability of relapse at 3 years after ABMT was 32% and 94% for K19-positive stage II/III and stage IV patients, respectively, versus 10% and 14% for K19-negative stage II/III and stage IV patients, respectively. The difference was significant for stage IV patients (two-tailed P = .0002). CONCLUSION It has been shown that PCR is a highly sensitive method to detect K19 message in the bone marrow. The incidence of K19 positivity in bone marrow increases significantly with advancing stage. In patients with breast cancer, especially metastatic breast cancer, undergoing HDCT and ABMT, the presence of K19 is associated with a poor prognosis.

scholarly journals Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy

2003 ◽  
Vol 32 (11) ◽  
pp. 1059-1064 ◽  
Author(s):  
F Viret ◽  
C Chabannon ◽  
D Sainty ◽  
D Genre ◽  
A Gonçalves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
High Dose Chemotherapy ◽  
Stage Ii ◽  
High Dose ◽  
Occult Tumor
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